array:24 [
  "pii" => "S225488742200042X"
  "issn" => "22548874"
  "doi" => "10.1016/j.rceng.2022.02.007"
  "estado" => "S300"
  "fechaPublicacion" => "2022-10-01"
  "aid" => "2016"
  "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)"
  "copyrightAnyo" => "2022"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "rev"
  "cita" => "Rev Clin Esp. 2022;222:486-95"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0014256522000182"
      "issn" => "00142565"
      "doi" => "10.1016/j.rce.2022.02.001"
      "estado" => "S300"
      "fechaPublicacion" => "2022-10-01"
      "aid" => "2016"
      "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "rev"
      "cita" => "Rev Clin Esp. 2022;222:486-95"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:1 [
        "total" => 0
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">REVISI&#211;N</span>"
        "titulo" => "Protocolo de diagn&#243;stico y seguimiento de pacientes adultos con neurofibromatosis tipo 1 en una unidad de referencia espa&#241;ola"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "486"
            "paginaFinal" => "495"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Diagnostic and follow-up protocol for adult patients with neurofibromatosis type 1 in a Spanish reference unit"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0010"
            "etiqueta" => "Figura 2"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr2.jpeg"
                "Alto" => 1929
                "Ancho" => 2925
                "Tamanyo" => 478317
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Propuesta de abordaje inicial y seguimiento de pacientes con neurofibromatosis tipo 1&#46; G-I&#58; gastrointestinal&#59; GIST&#58; tumor del estroma gastrointestinal&#59; HTA&#58; hipertensi&#243;n arterial&#59; NP&#58; neurofibroma plexiforme&#59; PET&#58; tomograf&#237;a por emisi&#243;n de positrones&#59; RM&#58; resonancia magn&#233;tica&#59; TC&#58; tomograf&#237;a computarizada&#59; TMVNP&#58; tumores malignos de la vaina nerviosa perif&#233;rica&#59; TVNP&#58; tumores de la vaina nerviosa perif&#233;rica&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "I&#46; Solares, D&#46; Vinal, M&#46; Morales-Conejo"
            "autores" => array:3 [
              0 => array:2 [
                "nombre" => "I&#46;"
                "apellidos" => "Solares"
              ]
              1 => array:2 [
                "nombre" => "D&#46;"
                "apellidos" => "Vinal"
              ]
              2 => array:2 [
                "nombre" => "M&#46;"
                "apellidos" => "Morales-Conejo"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S225488742200042X"
          "doi" => "10.1016/j.rceng.2022.02.007"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225488742200042X?idApp=WRCEE"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000182?idApp=WRCEE"
      "url" => "/00142565/0000022200000008/v1_202209290544/S0014256522000182/v1_202209290544/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:20 [
    "pii" => "S2254887422000467"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2022.03.005"
    "estado" => "S300"
    "fechaPublicacion" => "2022-10-01"
    "aid" => "2029"
    "copyright" => "The Authors"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "pgl"
    "cita" => "Rev Clin Esp. 2022;222:496-9"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Consensus Document</span>"
      "titulo" => "Executive summary on the treatment of type 2 diabetes mellitus in elderly or frail individuals&#46; 2022 update of the 2018 consensus document &#8220;Treatment of type 2 diabetes mellitus in the elderly&#8221;"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "496"
          "paginaFinal" => "499"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Resumen ejecutivo sobre el tratamiento de la diabetes mellitus tipo 2 en personas de edad avanzada o fr&#225;giles&#46; Actualizaci&#243;n 2022 del documento de consenso 2018 &#171;Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano&#187;"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 3806
              "Ancho" => 2925
              "Tamanyo" => 687974
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0005"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Strategy for starting and intensifying hypoglycemic treatment and therapy with full insulin regimens&#46; GLP-1ra&#58; GLP-1 receptor agonists&#59; CVD&#58; cardiovascular disease&#59; CKD&#58; chronic kidney disease&#59; FPG&#58; fasting plasma glucose&#59; PPG&#58; preprandial plasma glucose&#59; HF&#58; heart failure&#59; DPP-4i&#58; DPP-4 inhibitors&#59; SGLT-2i&#58; SGLT-2 inhibitors&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "F&#46; G&#243;mez-Peralta, F&#46;J&#46; Carrasco-S&#225;nchez, A&#46; P&#233;rez, J&#46; Escalada, F&#46; &#193;lvarez-Guisasola, C&#46; Miranda-Fern&#225;ndez-Santos, J&#46;J&#46; Mediavilla-Bravo, R&#46; G&#243;mez-Huelgas"
          "autores" => array:8 [
            0 => array:2 [
              "nombre" => "F&#46;"
              "apellidos" => "G&#243;mez-Peralta"
            ]
            1 => array:2 [
              "nombre" => "F&#46;J&#46;"
              "apellidos" => "Carrasco-S&#225;nchez"
            ]
            2 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "P&#233;rez"
            ]
            3 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Escalada"
            ]
            4 => array:2 [
              "nombre" => "F&#46;"
              "apellidos" => "&#193;lvarez-Guisasola"
            ]
            5 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "Miranda-Fern&#225;ndez-Santos"
            ]
            6 => array:2 [
              "nombre" => "J&#46;J&#46;"
              "apellidos" => "Mediavilla-Bravo"
            ]
            7 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "G&#243;mez-Huelgas"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256522000686"
        "doi" => "10.1016/j.rce.2022.03.004"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000686?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887422000467?idApp=WRCEE"
    "url" => "/22548874/0000022200000008/v1_202210061413/S2254887422000467/v1_202210061413/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2254887422000443"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2022.02.009"
    "estado" => "S300"
    "fechaPublicacion" => "2022-10-01"
    "aid" => "2024"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Rev Clin Esp. 2022;222:479-85"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Brief Original</span>"
      "titulo" => "Effect of HCV eradication on critical flicker frequency in HIV&#47;HCV coinfected patients with advanced cirrhosis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "479"
          "paginaFinal" => "485"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Efecto de la erradicaci&#243;n del VHC sobre la frecuencia cr&#237;tica de parpadeo en pacientes coinfectados por VIH&#47;VHC con cirrosis avanzada"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1903
              "Ancho" => 2516
              "Tamanyo" => 379949
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0005"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient flowchart&#46; CFF&#58; critical flicker frequency&#59; SVR&#58; sustained virologic response&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "V&#46; Honta&#241;&#243;n, J&#46; Gonz&#225;lez-Garc&#237;a, R&#46; Rubio-Mart&#237;n, C&#46; D&#237;ez, L&#46; Serrano-Morago, J&#46; Berenguer"
          "autores" => array:7 [
            0 => array:2 [
              "nombre" => "V&#46;"
              "apellidos" => "Honta&#241;&#243;n"
            ]
            1 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Gonz&#225;lez-Garc&#237;a"
            ]
            2 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "Rubio-Mart&#237;n"
            ]
            3 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "D&#237;ez"
            ]
            4 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Serrano-Morago"
            ]
            5 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Berenguer"
            ]
            6 => array:1 [
              "colaborador" => "on behalf of the ESCORIAL Study Group"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256522000261"
        "doi" => "10.1016/j.rce.2022.02.008"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000261?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887422000443?idApp=WRCEE"
    "url" => "/22548874/0000022200000008/v1_202210061413/S2254887422000443/v1_202210061413/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Diagnostic and follow-up protocol for adult patients with neurofibromatosis type 1 in a Spanish reference unit"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "486"
        "paginaFinal" => "495"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "I&#46; Solares, D&#46; Vinal, M&#46; Morales-Conejo"
        "autores" => array:3 [
          0 => array:3 [
            "nombre" => "I&#46;"
            "apellidos" => "Solares"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "D&#46;"
            "apellidos" => "Vinal"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:4 [
            "nombre" => "M&#46;"
            "apellidos" => "Morales-Conejo"
            "email" => array:1 [
              0 => "montserrat.morales@salud.madrid.org"
            ]
            "referencia" => array:4 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              3 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Unidad de Enfermedades Minoritarias y Errores Cong&#233;nitos del Metabolismo del Adulto&#44; Servicio de Medicina Interna&#44; Hospital Universitario 12 de Octubre&#44; Madrid&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Oncolog&#237;a M&#233;dica&#44; Hospital Universitario La Paz&#44; Madrid&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Instituto de Investigaci&#243;n Hospital 12 de Octubre &#40;i&#43;12&#41;&#44; Madrid&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Centro de Investigaci&#243;n Biom&#233;dica en Red de Enfermedades Raras &#40;CIBERER&#41;&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Protocolo de diagn&#243;stico y seguimiento de pacientes adultos con neurofibromatosis tipo 1 en una unidad de referencia espa&#241;ola"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2482
            "Ancho" => 2508
            "Tamanyo" => 527886
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic manifestations in individuals with neurofibromatosis type 1&#46; CNS&#58; central nervous system&#59; GIST&#58; gastrointestinal stromal tumor&#59; PNS&#58; peripheral nervous system&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0040" class="elsevierStylePara elsevierViewall">Neurofibromatosis &#40;NF&#41; is a heterogeneous group of neurocutaneous genetic disorders that are associated with the development of central and peripheral nervous system tumors&#46; There are three subtypes of NF&#58; NF1&#44; NF2&#44; and schwannomatosis<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">NF1 &#40;OMIM <a href="omim:#162200">&#35;162200</a>&#41; is the most prevalent form and represents 96&#37; of all cases&#46; This disease&#44; also known as von Recklinghausen&#8217;s disease&#44; is inherited with an autosomal dominant nature&#46; Its worldwide incidence is around one out of every 3000 individuals<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; NF1 is caused by a pathogenic variant of the NF1 tumor suppressor gene&#44; located on chromosome 17q11&#46;2&#46; In 90&#37; of cases&#44; this mutations leads to loss of function of the NF1 gene product&#44; neurofibromin&#44; which leads to an increase in RAS activity and promotes activation of the signaling cascade of the mitogen-activated protein kinase &#40;MEK&#41;&#47;extracellular signal-regulated kinase pathway&#44; which is frequently involved in the development of cancer<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; For this reason&#44; in addition to presenting with cutaneous&#44; ophthalmic&#44; and bone manifestations&#44; patients affected by NF1 have a high predisposition to developing both benign and malignant tumors including&#44; among others&#44; peripheral nerve sheath tumors&#44; gliomas&#44; breast cancer&#44; pheochromocytomas&#44; and gastrointestinal stromal tumors &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">NF2 and schwannomatosis are rare diseases compared to NF1&#44; representing 3&#37; and &#60;1&#37; of the total number of NF&#44; respectively&#46; NF2 tends to be associated with hypoacusis and vestibular dysfunction&#46; Multiple schwannomas are a distinctive characteristic of schwannomatosis that are habitually associated with intense pain<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In this review&#44; we summarize the diagnosis and main clinical characteristics and propose a screening and follow-up protocol for adult patients with NF1&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Diagnosis of NF1 by clinical criteria and genetic confirmation</span><p id="par0060" class="elsevierStylePara elsevierViewall">In 1988&#44; the clinical criteria for the diagnosis of NF1 were established at the United States of America&#8217;s National Institutes of Health consensus conference &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The gene associated with NF1 was discovered a few years after the publication of said consensus<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; The NF1 gene contains 60 exons and generates multiple isoforms through alternative splicing&#46; More than 1400 mutations in this gene have been described&#44; the majority of which are due to loss-of-function mutations<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Although the identification of NF1 mutations continues to be difficult due to the large size of the gene as well as the great variety of mutations that have been identified&#44; both tools provide benefits in the diagnosis and follow-up of these patients&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">1</span><p id="par0075" class="elsevierStylePara elsevierViewall">The genetic study can help diagnose cases of NF1 in which a clinical diagnosis cannot be established with certainly&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">2</span><p id="par0080" class="elsevierStylePara elsevierViewall">It has been described that certain types of mutations&#44; such as NF1 microdeletions&#44; entail a greater risk of developing malignant neoplasms&#44; thus the identification of these subjects is essential<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">3</span><p id="par0085" class="elsevierStylePara elsevierViewall">Fifty percent of NF1 mutations are <span class="elsevierStyleItalic">de novo</span>&#46; Therefore&#44; in half of the cases&#44; a genetic study in family members could help diagnose other carriers of the defect<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">4</span><p id="par0090" class="elsevierStylePara elsevierViewall">The identification of familial mutation in NF1 will facilitate genetic counseling and the selection of embryos in the case of wanting to become pregnant<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">5</span><p id="par0095" class="elsevierStylePara elsevierViewall">In addition&#44; the absence of a genetic confirmation does not rule out the disease in patients who meet clinical criteria&#44; given that the possibility of an unknown mutation in the NF1 locus or causal mutations in other loci of the genome cannot be ruled out<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46;</p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Cutaneous involvement</span><p id="par0100" class="elsevierStylePara elsevierViewall">Skin manifestations of NF1 are a hallmark of the disease and form part of the diagnostic criteria&#46; They consist of &#8220;caf&#233;-au-lait&#8221; macules&#44; freckling&#44; and neurofibromas&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">&#8220;Caf&#233;-au-lait&#8221; macules are pigmented macules with smooth borders that are chocolate brown in color&#46; They are present in 75&#37; of children and 90&#37; of adolescents and adults<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; These lesions do not pose a risk of malignant transformation&#44; tend to darken with exposure to sunlight&#44; and lighten with age&#46; Neither the size nor the number of &#8220;caf&#233;-au-lait&#8221; macules are directly related to greater disease severity<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">These lesions are present in approximately 10&#37; of the general population as well as in individuals with other genetic syndromes&#44; such as Silver-Russell dwarfism or LEOPARD&#44; Peutz-Jeghers&#44; Legius&#44; Noonan&#44; or McCune-Albright syndromes<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;14</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Freckles are mainly located in intertriginous areas such as the axillas&#44; where they are known as Crowe&#8217;s sign&#44; and the inguinal region&#46; They tend to appear in late childhood or puberty<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Neurofibromas are benign tumors consisting of Schwann cells&#44; perineurial cells&#44; fibroblasts&#44; mast cells&#44; axonal processes&#44; and an extracellular matrix composed of abundant collagen<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; These tumors are observed in almost all adults with NF1&#46; Although there is no risk of malignant transformation&#44; they can cause pruritus and pain as well as cosmetic problems&#46; In fact&#44; it is common for patients with NF1 to describe neurofibromas as the main drawback of their disease&#44; especially in cases in which resection is a challenge due to the numerous lesions they may present with<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to conduct a physical examination with a comprehensive skin evaluation annually&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ophthalmologic involvement</span><p id="par0130" class="elsevierStylePara elsevierViewall">Four main manifestations must be evaluated through ophthalmologic screening in patients with NF1&#58; Lisch nodules&#44; optic pathway gliomas&#44; sphenoid dysplasia&#44; and orbital plexiform neurofibromas &#40;PN&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In most adult patients with NF1&#44; small melanocytic hamartomas can be identified in the iris on a slit lamp examination&#46; These lesions&#44; called Lisch nodules&#44; are characteristic of this disease and do not interfere with vision&#46; They should not be confused with iris nevi&#44; which are common in healthy individuals<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Presence of an optic glioma should be suspected in patients with NF1 who develop unilateral proptosis&#44; visual field defects&#44; strabismus&#44; an afferent pupillary defect&#44; or optic disc edema&#47;atrophy&#46; In addition&#44; tumors with a chiasmatic location may manifest in the form of early puberty<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Around 15&#37; of patients with NF1 develop optic gliomas&#44; but in most cases&#44; they do not cause any clinical repercussions&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Orbital neurofibromas are often accompanied by skull deformities&#46; A skeletal anomaly characteristic of NF1 is the partial or complete absence of the greater wing of the sphenoid bone&#44; with the consequent communication between the medial cranial fossa and the socket&#46; This defect leads to the temporal lobe being able to herniate towards the socket and cause pulsatile exophthalmos or&#44; less often&#44; the orbital content can herniate in the medial cranial fossa and cause enophthalmos<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to conduct a comprehensive ophthalmologic examination &#40;color vision&#44; visual field&#44; ocular motility&#44; pupillary reflexes&#44; slit lamp examination&#44; and fundoscopy&#41; at the time of diagnosis followed by annual exams&#46; Radiological follow-up is only ordered in the case of presenting with indicative symptoms<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Skeletal involvement</span><p id="par0160" class="elsevierStylePara elsevierViewall">Approximately 50&#37; of patients have significant musculoskeletal manifestations&#44; the most common of which are scoliosis and congenital tibial dysplasia&#46; Other bone manifestations include short height&#44; pseudoarthrosis&#44; massive subperiosteal bone proliferation&#44; and intraosseous cystic lesions that can resemble a malignant neoplasm<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; It has also been described that young subjects with NF1 have reduced bone mass&#44; especially in the lumbar spine area&#44; due to the loss of function of neurofibromin&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to follow-up on the bone mineral profile through blood levels of vitamin D and PTH annually together with a densitometric study every three to five years<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Cardiovascular involvement</span><p id="par0170" class="elsevierStylePara elsevierViewall">The term &#8220;NF1 vasculopathy&#8221; has recently been coined to describe the vascular lesions these patients present with&#46; Although the frequency of this type of disease is difficult to define because it is not routinely screened for&#44; its prevalence is estimated to be from 0&#46;4&#37;&#8211;6&#46;4&#37;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46; This entity encompasses aneurysms&#44; stenosis&#44; or malformations of medium- and large-caliber arteries and veins and cardiovascular malformations &#40;pulmonary stenosis and coarctation of the aorta&#41;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#46; Therefore&#44; it is recommendable to order an echocardiogram in the first evaluation of patients with NF1&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Stenosis of the renal artery occurs in approximately 2&#37; of the population with NF1 and its diagnosis must be considered in hypertensive patients or those in whom an abdominal bruit is identified&#46; Although the gold standard for the diagnosis of renal artery stenosis is renal arteriography&#44; the study can be started by means of less invasive tests&#44; such as a Doppler ultrasound or magnetic resonance &#40;MR&#41; angiography<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Pheochromocytoma is an uncommon cause of hypertension&#44; but it occurs in around 2&#37; of adult patients with NF1&#46; Its clinical presentation often includes palpitations&#44; headache&#44; dizziness&#44; or sweating in addition to hypertension<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> Blood pressure must be periodically monitored at home and must be below 140&#47;90&#8239;mmHg or 130&#47;85 in individuals with target organ lesions or diabetes&#46; The presence of hypertension makes it necessary to rule out secondary causes such as renal artery stenosis or the presence of pheochromocytoma&#44; especially in the case of young patients&#44; pregnant women&#44; or elderly individuals with refractory hypertension&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Neuropsychological involvement</span><p id="par0190" class="elsevierStylePara elsevierViewall">Neurocognitive problems are the most common neurological complication in individuals with NF1 and include both an intellectual quotient in the medium-low range and specific cognitive deficits in the areas of attention&#44; executive function&#44; and language skills&#46; A greater frequency of autism spectrum disorders has also been described<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#8211;30</span></a>&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Therefore&#44; in order to increase their possibilities of academic&#44; occupational&#44; and social success as adults&#44; patients with NF1 must be evaluated from an early age by pediatric neuropsychologists&#44; physical therapists&#44; and speech and&#47;or occupational therapists&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">What&#8217;s more&#44; epilepsy is present in approximately 4&#37;&#8211;6&#37; of individuals of NF1 and is commonly related to the development of central nervous system neoplasms or with an underlying cortical dysgenesis<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#46; They often present with partial seizures and it is relatively simple to control with anti-seizure treatment<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Although the risk of dementia in NF1 is little described&#44; recent studies link this entity with a greater predisposition toward the development of cognitive impairment&#44; especially Alzheimer&#8217;s disease<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to perform a brain MR imaging test in all patients with NF1 who present with an initial epileptic seizure and in those with new-onset focal neurological signs&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Oncological involvement</span><p id="par0215" class="elsevierStylePara elsevierViewall">The incidence of cancer in patients with NF1 is five to ten times greater than in the general population&#44; with a cumulative risk of cancer of 40&#37; at 50 years of age<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a>&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Neurofibromas are the most prevalent benign tumors whereas low-grade gliomas and malignant peripheral nerve sheath tumors &#40;MPNST&#41; are the most common malignant neoplasms<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46; Likewise&#44; cancer is the most frequent cause of death in these patients<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#46; MPNST&#44; breast cancer&#44; and high-grade gliomas the most typical manifestations of NF1 in adulthood &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0225" class="elsevierStylePara elsevierViewall">A physical examination and patient education in order to detect warning signs are the fundamental pillars in follow-up&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Plexiform neurofibromas</span><p id="par0230" class="elsevierStylePara elsevierViewall">PN are benign tumors of the peripheral nerve sheath that occur in up to 50&#37; of patients with NF1<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#46; They can be superficial or deep&#46; They tend to be present at birth and grow more notably during the first decade of life<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Despite their benign behavior&#44; they are an important cause of morbidity due to local invasion&#44; including pain&#44; motor dysfunction&#44; and vision loss<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&#46; Furthermore&#44; there is a risk of malignant degeneration to MPNST<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&#46; Symptomatic treatment is surgical but&#44; on many occasions&#44; it is technically complicated<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&#46; In patients with inoperable PN&#44; MEK inhibitors and cabozantinib have demonstrated clinical benefits such as a reduction in tumor size and pain intensity and an improvement in quality of life&#44; with a manageable toxicity profile<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; Selumetinib&#44; a selective MEK inhibitor<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#44; was approved by the Food and Drug Administration in May 2020 for this scenario&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Malignant peripheral nerve sheath tumor</span><p id="par0240" class="elsevierStylePara elsevierViewall">MPNST is an aggressive type of soft tissue sarcoma that is very uncommon in the general population&#44; but observed in 10&#37;&#8211;15&#37; of patients with NF1<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46; In patients with NF1&#44; MPNST occurs almost exclusively on PN&#46; They are locally aggressive neoplasms with a high potential for metastasis&#46; MPNST are one of the principal causes of mortality<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;43</span></a>&#46; The presence of internal PN<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&#44; NF1 locus germline microdeletion<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#44; and prior radiation are risk factors for its onset<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">45&#44;46</span></a>&#46; An MPNST are most often located on the limbs and trunk<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;48</span></a>&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">An MPNST is suspected when there is a brusque change in the pre-existing PN&#44; whether that be an increase in pain&#44; the size of the tumor mass&#44; or progression of neurological impairment<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a>&#46; When there is clinical suspicion&#44; a diffusion-weighted MR imaging test and&#47;or a PET-computed tomography &#40;CT&#41; scan must be performed<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&#46; The definitive diagnosis of MPNST requires histological confirmation&#46; Treatment of MPNST must be performed by a multidisciplinary team in centers with experience in soft tissue sarcomas<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a>&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation&#58;</span> There is no consensus on screening asymptomatic patients with NF1<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a>&#46; Therefore&#44; some reference centers have established their own screening protocols with whole-body diffusion-weighted MR imaging tests or PET-CT scans in patients at &#8220;high risk&#8221; for malignant transformation&#46; Some clinical guidelines<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> recommend performing whole-body MR imaging in patients between 16&#8211;20 years of age before their transition to the adult unit in order to establish the baseline internal PN burden&#44; given that somatic growth may have ended by that time<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">53&#8211;55</span></a>&#46; This management requires prospective validation&#46; In centers where whole-body MR imaging is not available&#44; performing a brain and neuroaxis MR imaging could be considered<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Brain tumors</span><p id="par0255" class="elsevierStylePara elsevierViewall">Central nervous system tumors as a whole are the most common neoplasms in patients with NF1<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a> and represent one of the most habitual causes of mortality<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">The most common tumors are optic nerve gliomas&#44; which are usually low-grade pilocytic astrocytomas&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> They occur in 15&#37; of children younger than six years of age and are exceptional after adolescence<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a>&#46; They may entail a decrease in visual acuity&#44; abnormalities in discerning colors&#44; abnormal pupillary function&#44; and proptosis<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a>&#46; The gold standard for diagnosis is MR imaging&#44; although optical coherence tomography has shown promising results&#46; The initial treatment tends to include an observation period&#44; if possible&#46; If there is progression&#44; treatment with chemotherapy or surgery is considered&#46; Radiotherapy tends to be avoided due to the risk of secondary tumors<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Patients with NF1 also tend to be at greater risk of developing low-grade astrocytomas in other locations &#40;5&#37;&#41;&#44; included the basal ganglia&#44; cerebellum&#44; or brain stem&#44; as well as high-grade gliomas &#40;1&#37;&#8211;2&#37;&#41; at younger ages<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46; The most common clinical presentation is an increase in intracranial pressure&#44; although they tend to be asymptomatic<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a>&#46; The treatment is similar to that of patients without NF1<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&#46; Treatment with MEK inhibitors such as selumetinib&#44; trametinib&#44; and binimetinib is showing promising results<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a>&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to screen for optic nerve gliomas by means of ophthalmologic examinations every six or 12 months until eight years of age &#40;the age of greatest risk&#41; and then every two years until 18 years of age&#44; after which its onset is extremely rare<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;60</span></a>&#46; Screening for other low-grade astrocytomas is not routinely performed&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Breast cancer in patients with NF1</span><p id="par0275" class="elsevierStylePara elsevierViewall">Women with NF1 have a greater risk of developing breast cancer and at an earlier age than the general population<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35&#44;63&#44;64</span></a>&#46; Women younger than 50 years with NF1 have a five-fold risk of developing breast cancer&#44; present with more advanced stage cancer upon diagnosis&#44; and have greater mortality<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;64</span></a>&#46; The risk of breast cancer in men with NF1 appears to be low<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">65&#8211;68</span></a>&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation&#58;</span> Clinical guidelines<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">63&#44;69</span></a> recommend screening for breast cancer starting at 30 years of age and consider a breast MR imaging test with contrast between 30 and 50 years of age&#46; Screening can begin earlier according to family history&#44; starting it five to ten years before the earliest age of breast cancer diagnosis in the family<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">63&#44;69</span></a>&#46; It is important to highlight the risk of false positives on imaging tests and their difficult interpretation due to the presence of mammary neurofibromas<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a>&#46; At present&#44; there is not enough evidence to recommend a radical mastectomy&#44; although it could be considered based on family history<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Pheochromocytomas</span><p id="par0285" class="elsevierStylePara elsevierViewall">Pheochromocytomas are catecholamine-secreting tumors which emerge on the chromaffin cells of the adrenal medulla&#46; They are rare in the general population&#44; but their incidence increases in patients with NF1<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&#46; They are diagnosed in the fourth decade of life and their location tends to be adrenal<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">The most typical clinical manifestation is the classic triad of paroxysmal episodes of headache&#44; sweating&#44; and tachycardia&#46; However&#44; the most common symptom that tends to lead to a diagnosis is new-onset hypertension<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a>&#46; When faced with these symptoms&#44; a 24-h urinary fractionated metanephrines test or a plasma free metanephrines and methoxytyramine test should be ordered<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a>&#46; In case of biochemical confirmation&#44; an abdominal CT scan or MR imaging test will be performed&#46; For more information on diagnosis and treatment&#44; specific clinical guidelines should be consulted<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">72&#44;73</span></a>&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> Given the lack of randomized studies on the efficacy of biochemical or imaging test screening for detecting pheochromocytomas in asymptomatic patients with NF1&#44; the main clinical guidelines do not recommend it&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Gastrointestinal stromal tumors</span><p id="par0300" class="elsevierStylePara elsevierViewall">Gastrointestinal stromal tumors are uncommon mesenchymal neoplasms of the gastrointestinal tract which&#44; despite their low frequency in patients with NF1 &#40;0&#46;2&#37;&#8211;1&#46;2&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a>&#44; are more common than in the general population &#40;standardized incidence ratio &#40;SIR&#41;&#58; 51&#46;2&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#41;&#46; In patients with NF1&#44; they are predominantly located in the small intestine &#40;65&#37; in the jejunum and ileum&#41;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a>&#46; Somatic mutations in KIT or PDGFRA are rare&#44; unlike sporadic cases<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">74&#44;75</span></a>&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">The most common clinical manifestations tend to be gastrointestinal bleeding or anemia&#46; The diagnosis is made by means of a CT scan with contrast and a biopsy&#44; when possible&#46; Treatment is surgical&#44; except in metastatic disease&#46; In that scenario&#44; kinase-tyrosine inhibitors have been demonstrated to prolong survival<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a>&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation&#58;</span> There are currently no randomized studies which justify screening in asymptomatic patients with NF1&#44; but performing an abdominal or thoracic-abdominal-pelvic CT scan with contrast is recommended when there is clinical suspicion<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a>&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Other tumors</span><p id="par0315" class="elsevierStylePara elsevierViewall">Other characteristic malignant neoplasms in patients with NF1 in pediatric ages are embryonal rhabdomyosarcoma<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#44; with a mean age of onset of two years&#44; and myelomonocytic leukemia<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a>&#46; Patients with NF1 are at increased risk of developing other tumors at earlier ages and with a worse prognosis compared to the general population&#46; Of note among them are undifferentiated pleomorphic sarcoma &#40;odds ratio &#40;OR&#41;&#58; 23&#41; and other sarcomas&#44; melanoma &#40;OR&#58; 3&#46;9&#41;&#44; and ovarian cancer &#40;OR&#58; 5&#46;6&#41;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation&#58;</span> There is currently no evidence to recommend biochemical or radiological screening for other tumors&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Algorithm for transfer to the adult unit and recommendations for follow-up</span><p id="par0325" class="elsevierStylePara elsevierViewall">Our proposal for the management of adult patients with NF1 is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; Transferring patients with NF1 to the adult rare disease unit at 16&#8211;18 years of age is proposed&#46; A neuropsychiatric and ophthalmic evaluation will be conducted both if it has not been performed in these patients before and in those diagnosed in adult ages&#46; Genetic counseling will be provided to all recently diagnosed patients and at the time they wish to become pregnant&#46; A baseline echocardiogram and MR imaging test of the skull will be ordered&#46; Optionally&#44; a whole-body MR imaging test can be requested in order to establish the baseline internal neurofibroma burden&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0330" class="elsevierStylePara elsevierViewall">Annual follow-up that includes a skin evaluation&#44; blood pressure monitoring&#44; and a neurological and ophthalmologic examination is proposed&#46; An annual blood test will be performed to evaluate vitamin D levels and a densitometric scan will be performed every three to five years&#46; An annual mammogram will be performed in women starting at 30 years of age&#46; In patients at high risk for malignant transformation of PN&#44; a periodic whole-body MR imaging test or PET-CT scan should be evaluated&#46; There is currently no consensus among specialists or robust prospective evidence on the utility of imaging screening and the type of test that should be performed in asymptomatic patients&#46; The suitability of a whole-body MR imaging as a screening method and the periodicity with which it should be performed in high-risk patients is currently under study<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">78</span></a>&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">In each consultation&#44; focus will be placed on warning signs such as blood pressure&#59; neurological abnormalities&#59; psychiatric abnormalities&#59; and changes in pain&#44; size&#44; or progression of neurological impairment in previous neurofibromas&#46; When alarm signs or symptoms are detected&#44; action will be taken in accordance with the algorithm shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; This algorithm is based on the main clinical guidelines for the management of patients with NF1<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;14&#44;27&#44;53</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;60&#44;63</span></a>&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusions</span><p id="par0340" class="elsevierStylePara elsevierViewall">NF1 is a disease that has multisystemic involvement which entails significant morbidity and mortality&#46; In these patients&#44; it is essential to provide adequate genetic counseling&#59; ensure the early detection of possible neuropsychological&#44; cardiovascular&#44; and oncological complications&#44; among others&#59; and offer a specific therapeutic approach in centers with experience in this disease&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0345" class="elsevierStylePara elsevierViewall">This research has not received specific grants from agencies in the public&#44; commercial&#44; or non-profit sectors&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interest</span><p id="par0350" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:17 [
        0 => array:3 [
          "identificador" => "xres1778589"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1561541"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1778590"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1561540"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Diagnosis of NF1 by clinical criteria and genetic confirmation"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Cutaneous involvement"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Ophthalmologic involvement"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Skeletal involvement"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Cardiovascular involvement"
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Neuropsychological involvement"
        ]
        11 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Oncological involvement"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Plexiform neurofibromas"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Malignant peripheral nerve sheath tumor"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Brain tumors"
            ]
            3 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Breast cancer in patients with NF1"
            ]
            4 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Pheochromocytomas"
            ]
            5 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Gastrointestinal stromal tumors"
            ]
            6 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Other tumors"
            ]
          ]
        ]
        12 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Algorithm for transfer to the adult unit and recommendations for follow-up"
        ]
        13 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conclusions"
        ]
        14 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Funding"
        ]
        15 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conflicts of interest"
        ]
        16 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2021-10-14"
    "fechaAceptado" => "2022-02-07"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1561541"
          "palabras" => array:3 [
            0 => "Neurofibromatosis"
            1 => "Plexiform neurofibroma"
            2 => "<span class="elsevierStyleItalic">Caf&#233;-au-lait</span> spots"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1561540"
          "palabras" => array:3 [
            0 => "Neurofibromatosis"
            1 => "Neurofibroma plexiforme"
            2 => "Manchas &#171;caf&#233; con leche&#187;"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Neurofibromatosis type 1 &#40;NF1&#41; is one of the most common genetic neurocutaneous disorders&#46; The hallmark of this disease is skin lesions in the form of caf&#233;-au-lait spots&#44; ephelides&#44; and the characteristic cutaneous neurofibromas&#46; Other common manifestations include bone abnormalities&#44; &#8220;NF1 vasculopathy&#44;&#8221; and neurocognitive disorders&#46; In addition&#44; patients are at an increased risk for a wide variety of malignant neoplasms&#44; including the malignant transformation of plexiform neurofibromas&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">It is necessary to know the various clinical characteristics of this disorder and to provide an early&#44; multidisciplinary follow-up and treatment approach in order to provide optimal care to these patients&#44; who present with a multisystemic disease that is potentially severe&#46; This review summarizes the diagnosis and main clinical characteristics and suggests a protocol for screening and follow-up of adult patients with NF1&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La neurofibromatosis tipo 1 &#40;NF1&#41; es uno de los trastornos gen&#233;ticos neurocut&#225;neos m&#225;s frecuentes&#46; La caracter&#237;stica de esta enfermedad es la afectaci&#243;n cut&#225;nea en forma de manchas caf&#233; con leche&#44; ef&#233;lides y los caracter&#237;sticos neurofibromas cut&#225;neos&#46; Otras manifestaciones frecuentes incluyen las alteraciones &#243;seas&#44; la &#171;vasculopat&#237;a por NF1&#187; y los problemas neurocognitivos&#46; Adem&#225;s&#44; los pacientes tienen m&#225;s riesgo de padecer una gran variedad de neoplasias malignas&#44; incluida la transformaci&#243;n maligna de neurofibromas plexiformes&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Para ser capaces de brindar una atenci&#243;n &#243;ptima a estos pacientes&#44; que presentan una afectaci&#243;n multisist&#233;mica y potencialmente grave&#44; es necesario conocer las diversas caracter&#237;sticas cl&#237;nicas de este trastorno&#44; as&#237; como propiciar un seguimiento y abordaje terap&#233;utico precoz y multidisciplinar&#46; En esta revisi&#243;n&#44; resumimos el diagn&#243;stico&#44; las principales caracter&#237;sticas cl&#237;nicas y proponemos un protocolo de cribado y seguimiento de pacientes adultos con NF1&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Solares I&#44; Vinal D&#44; Morales-Conejo M&#46; Protocolo de diagn&#243;stico y seguimiento de pacientes adultos con neurofibromatosis tipo 1 en una unidad de referencia espa&#241;ola&#46; Rev Clin Esp&#46; 2022&#59;222&#58;486&#8211;495&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2482
            "Ancho" => 2508
            "Tamanyo" => 527886
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic manifestations in individuals with neurofibromatosis type 1&#46; CNS&#58; central nervous system&#59; GIST&#58; gastrointestinal stromal tumor&#59; PNS&#58; peripheral nervous system&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1929
            "Ancho" => 2925
            "Tamanyo" => 516944
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Proposal for the initial approach and follow-up on patients with neurofibromatosis type 1&#46; G-I&#58; gastrointestinal&#59; GIST&#58; gastrointestinal stromal tumor&#59; HT&#58; hypertension&#59; PN&#58; plexiform neurofibroma&#59; PET&#58; positron emission tomography&#59; MR&#58; magnetic resonance&#59; CT&#58; computed tomography&#59; MPNST&#58; malignant peripheral nerve sheath tumor&#59; PNST&#58; peripheral nerve sheath tumor&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">NF1&#58; neurofibromatosis type 1&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Two or more of the following clinical characteristics are enough to establish a diagnosis of neurofibromatosis type 1&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0005" class="elsevierStylePara elsevierViewall">Six or more &#8220;caf&#233;-au-lait&#8221; macules with a diameter greater than 5&#8239;mm in prepubescent subjects or 15&#8239;mm in postpubescent subjects</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0010" class="elsevierStylePara elsevierViewall">Two or more neurofibromas of any type or a plexiform neurofibroma</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0015" class="elsevierStylePara elsevierViewall">Freckling in the axillary or inguinal region</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0020" class="elsevierStylePara elsevierViewall">Optic nerve glioma</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0025" class="elsevierStylePara elsevierViewall">Two or more Lisch nodules &#40;iris hamartomas&#41;</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">A distinctive bone lesion such as sphenoid dysplasia or cortical bone thinning with or without pseudoarthrosis</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">An immediate family member &#40;parents&#44; siblings&#44; or children&#41; with NF1 according to the above criteria</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#8220;Classic&#8221; diagnostic criteria for neurofibromatosis type 1 from the United States of America&#8217;s National Institute of Health&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">MPNST&#58; malignant peripheral nerve sheath tumor&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Birth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Childhood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adolescence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adult age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8220;Caf&#233;-au-lait&#8221; macules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Learning delays&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Freckling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MPNST&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Orbital dysplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Motor or speech delay&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lisch nodules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Breast cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tibial dysplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Attention deficit disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Scoliosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">High-grade glioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pseudoarthrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autism spectrum disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cutaneous neurofibromas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Plexiform neurofibromas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Optic nerve glioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paraspinal neurofibromas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brainstem glioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Development of clinical characteristics in patients with neurofibromatosis type 1&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:78 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis&#58; a review of NF1&#44; NF2&#44; and schwannomatosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;L&#46; Kresak"
                            1 => "M&#46; Walsh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1055/s-0036-1579766"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr Genet"
                        "fecha" => "2016"
                        "volumen" => "5"
                        "paginaInicial" => "98"
                        "paginaFinal" => "104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27617150"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Birth incidence and prevalence of tumor-prone syndromes&#58; estimates from a UK family genetic register service"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;G&#46; Evans"
                            1 => "E&#46; Howard"
                            2 => "C&#46; Giblin"
                            3 => "T&#46; Clancy"
                            4 => "H&#46; Spencer"
                            5 => "S&#46;M&#46; Huson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ajmg.a.33139"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med Genet A"
                        "fecha" => "2010"
                        "volumen" => "152A"
                        "paginaInicial" => "327"
                        "paginaFinal" => "332"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20082463"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas&#58; a comprehensive review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I&#46; Solares"
                            1 => "D&#46; Vi&#241;al"
                            2 => "M&#46; Morales-Conejo"
                            3 => "N&#46; Rodriguez-Salas"
                            4 => "J&#46; Feliu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.esmoop.2021.100223"
                      "Revista" => array:5 [
                        "tituloSerie" => "ESMO Open"
                        "fecha" => "2021"
                        "volumen" => "6"
                        "paginaInicial" => "100223"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34388689"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type 1&#58; a multidisciplinary approach to care"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;C&#46; Hirbe"
                            1 => "D&#46;H&#46; Gutmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1474-4422(14)70063-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Neurol"
                        "fecha" => "2014"
                        "volumen" => "13"
                        "paginaInicial" => "834"
                        "paginaFinal" => "843"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25030515"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current understanding of neurofibromatosis type 1&#44; 2&#44; and schwannomatosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Tamura"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/ijms22115850"
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Mol Sci"
                        "fecha" => "2021"
                        "volumen" => "22"
                        "paginaInicial" => "5850"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34072574"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Neurofibromatosis&#46; Conference statement&#46; National Institutes of Health Consensus Development Conference"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Neurol"
                        "fecha" => "1988"
                        "volumen" => "45"
                        "paginaInicial" => "575"
                        "paginaFinal" => "578"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3128965"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Viskochil"
                            1 => "A&#46;M&#46; Buchberg"
                            2 => "G&#46; Xu"
                            3 => "R&#46;M&#46; Cawthon"
                            4 => "J&#46; Stevens"
                            5 => "R&#46;K&#46; Wolff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0092-8674(90)90252-a"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "1990"
                        "volumen" => "62"
                        "paginaInicial" => "187"
                        "paginaFinal" => "192"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1694727"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A RASopathy gene commonly mutated in cancer&#58; the neurofibromatosis type 1 tumour suppressor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "N&#46; Ratner"
                            1 => "S&#46;J&#46; Miller"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrc3911"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Cancer"
                        "fecha" => "2015"
                        "volumen" => "15"
                        "paginaInicial" => "290"
                        "paginaFinal" => "301"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25877329"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated risk for MPNST in NF1 microdeletion patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; De Raedt"
                            1 => "H&#46; Brems"
                            2 => "P&#46; Wolkenstein"
                            3 => "D&#46; Vidaud"
                            4 => "S&#46; Pilotti"
                            5 => "F&#46; Perrone"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/374821"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2003"
                        "volumen" => "72"
                        "paginaInicial" => "1288"
                        "paginaFinal" => "1292"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12660952"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;E&#46; Ferner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.ejhg.5201676"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Hum Genet"
                        "fecha" => "2007"
                        "volumen" => "15"
                        "paginaInicial" => "131"
                        "paginaFinal" => "138"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16957683"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is it time to change the neurofibromatosis 1 diagnostic criteria&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46; Tadini"
                            1 => "D&#46; Milani"
                            2 => "F&#46; Menni"
                            3 => "L&#46; Pezzani"
                            4 => "C&#46; Sabatini"
                            5 => "S&#46; Esposito"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejim.2014.04.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Intern Med"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "506"
                        "paginaFinal" => "510"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24784952"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Type I neurofibromatosis&#58; case report and review of the literature focused on oral and cutaneous lesions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Buchholzer"
                            1 => "R&#46; Verdeja"
                            2 => "T&#46; Lombardi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/dermatopathology8010003"
                      "Revista" => array:5 [
                        "tituloSerie" => "Dermatopathology &#40;Basel&#41;"
                        "fecha" => "2021"
                        "volumen" => "8"
                        "paginaInicial" => "17"
                        "paginaFinal" => "24"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pathoetiology of neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "E&#46;M&#46; Jouhilahti"
                            1 => "S&#46; Peltonen"
                            2 => "A&#46;M&#46; Heape"
                            3 => "J&#46; Peltonen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajpath.2010.12.056"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Pathol"
                        "fecha" => "2011"
                        "volumen" => "178"
                        "paginaInicial" => "1932"
                        "paginaFinal" => "1939"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21457932"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines for the diagnosis and management of individuals with neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;E&#46; Ferner"
                            1 => "S&#46;M&#46; Huson"
                            2 => "N&#46; Thomas"
                            3 => "C&#46; Moss"
                            4 => "H&#46; Willshaw"
                            5 => "D&#46;G&#46; Evans"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/jmg.2006.045906"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Med Genet"
                        "fecha" => "2007"
                        "volumen" => "44"
                        "paginaInicial" => "81"
                        "paginaFinal" => "88"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17105749"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis 1&#58; clinical manifestations and diagnostic criteria"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;M&#46; Friedman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/088307380201700802"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Child Neurol"
                        "fecha" => "2002"
                        "volumen" => "17"
                        "paginaInicial" => "548"
                        "paginaFinal" => "651"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12403552"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The development of cutaneous neurofibromas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;M&#46; Jouhilahti"
                            1 => "S&#46; Peltonen"
                            2 => "T&#46; Callens"
                            3 => "E&#46; Jokinen"
                            4 => "A&#46;M&#46; Heape"
                            5 => "L&#46; Messiaen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajpath.2010.10.041"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Pathol"
                        "fecha" => "2011"
                        "volumen" => "178"
                        "paginaInicial" => "500"
                        "paginaFinal" => "505"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21281783"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cutaneous neurofibromas in the genomics era&#58; current understanding and open questions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;J&#46; Allaway"
                            1 => "S&#46;J&#46;C&#46; Gosline"
                            2 => "S&#46; La Rosa"
                            3 => "P&#46; Knight"
                            4 => "A&#46; Bakker"
                            5 => "J&#46; Guinney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41416-018-0073-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Cancer"
                        "fecha" => "2018"
                        "volumen" => "118"
                        "paginaInicial" => "1539"
                        "paginaFinal" => "1548"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29695767"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ophthalmological assessment of children with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Cassiman"
                            1 => "E&#46; Legius"
                            2 => "W&#46; Spileers"
                            3 => "I&#46; Casteels"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00431-013-2035-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Pediatr"
                        "fecha" => "2013"
                        "volumen" => "172"
                        "paginaInicial" => "1327"
                        "paginaFinal" => "1333"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23708214"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Orbitotemporal neurofibromatosis&#58; classification and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;H&#46; Erb"
                            1 => "N&#46; Uzcategui"
                            2 => "R&#46;F&#46; See"
                            3 => "M&#46;A&#46; Burnstine"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/01676830600987227"
                      "Revista" => array:6 [
                        "tituloSerie" => "Orbit"
                        "fecha" => "2007"
                        "volumen" => "26"
                        "paginaInicial" => "223"
                        "paginaFinal" => "228"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18097958"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Optic pathway gliomas in children with neurofibromatosis 1&#58; consensus statement from the NF1 Optic Pathway Glioma Task Force"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46; Listernick"
                            1 => "D&#46;N&#46; Louis"
                            2 => "R&#46;J&#46; Packer"
                            3 => "D&#46;H&#46; Gutmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ana.410410204"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Neurol"
                        "fecha" => "1997"
                        "volumen" => "41"
                        "paginaInicial" => "143"
                        "paginaFinal" => "149"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9029062"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Orthopaedic manifestations of neurofibromatosis in children&#58; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;G&#46; Vitale"
                            1 => "A&#46; Guha"
                            2 => "D&#46;L&#46; Skaggs"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00003086-200208000-00013"
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Orthop Relat Res"
                        "fecha" => "2002"
                        "paginaInicial" => "107"
                        "paginaFinal" => "118"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20676810"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Generalized metabolic bone disease in neurofibromatosis type I"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Brunetti-Pierri"
                             …5
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ymgme.2007.12.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Genet Metab"
                        "fecha" => "2008"
                        "volumen" => "94"
                        "paginaInicial" => "105"
                        "paginaFinal" => "111"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vascular abnormalities in patients with neurofibromatosis syndrome type I&#58; clinical spectrum&#44; management&#44; and results"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jvs.2007.03.055"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Vasc Surg"
                        "fecha" => "2007"
                        "volumen" => "46"
                        "paginaInicial" => "475"
                        "paginaFinal" => "484"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1096-8628(20001113)95:2<108::aid-ajmg4>3.0.co;2-0"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Med Genet"
                        "fecha" => "2000"
                        "volumen" => "95"
                        "paginaInicial" => "108"
                        "paginaFinal" => "117"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0085253815302027"
                          "estado" => "S300"
                          "issn" => "00852538"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.106.174526"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2006"
                        "volumen" => "113"
                        "paginaInicial" => "e463"
                        "paginaFinal" => "e654"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of renal vascular disease in neurofibromatosis type 1 and the role of percutaneous transluminal angioplasty"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/17.7.1235"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2002"
                        "volumen" => "17"
                        "paginaInicial" => "1235"
                        "paginaFinal" => "1240"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular disease in neurofibromatosis 1&#58; report of the NF1 Cardiovascular Task Force"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00125817-200205000-00002"
                      "Revista" => array:7 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2002"
                        "volumen" => "4"
                        "paginaInicial" => "105"
                        "paginaFinal" => "111"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0016508508016065"
                          "estado" => "S300"
                          "issn" => "00165085"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Behaviour in children with neurofibromatosis type 1&#58; cognition&#44; executive function&#44; attention&#44; emotion&#44; and social competence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1469-8749.2012.04399.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dev Med Child Neurol"
                        "fecha" => "2013"
                        "volumen" => "55"
                        "paginaInicial" => "111"
                        "paginaFinal" => "125"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The nature and frequency of cognitive deficits in children with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/01.wnl.0000179303.72345.ce"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2005"
                        "volumen" => "65"
                        "paginaInicial" => "1037"
                        "paginaFinal" => "1044"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selective impairment of the executive attentional network in adult patients with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/WNR.0000000000001275"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuroreport"
                        "fecha" => "2019"
                        "volumen" => "30"
                        "paginaInicial" => "921"
                        "paginaFinal" => "926"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epilepsy in neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/08830738030180050501"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Child Neurol"
                        "fecha" => "2003"
                        "volumen" => "18"
                        "paginaInicial" => "338"
                        "paginaFinal" => "342"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epilepsy in individuals with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/epi.12348"
                      "Revista" => array:6 [
                        "tituloSerie" => "Epilepsia"
                        "fecha" => "2013"
                        "volumen" => "54"
                        "paginaInicial" => "1810"
                        "paginaFinal" => "1814"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased risk for dementia in neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41436-021-01261-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2021"
                        "volumen" => "23"
                        "paginaInicial" => "2219"
                        "paginaFinal" => "2222"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Distinctive cancer associations in patients with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2015.65.3576"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2016"
                        "volumen" => "34"
                        "paginaInicial" => "1978"
                        "paginaFinal" => "1986"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of cancer prevalence in patients with neurofibromatosis type 1 at an academic cancer center vs&#46; in the general population from 1985 to 2020"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamanetworkopen.2021.0945"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA Netw Open"
                        "fecha" => "2021"
                        "volumen" => "4"
                        "paginaInicial" => "e210945"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0085253815303598"
                          "estado" => "S300"
                          "issn" => "00852538"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality in neurofibromatosis 1&#58; in North West England&#58; an assessment of actuarial survival in a region of the UK since 1989"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ejhg.2011.113"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Hum Genet"
                        "fecha" => "2011"
                        "volumen" => "19"
                        "paginaInicial" => "1187"
                        "paginaFinal" => "1191"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrdp.2017.4"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Rev Dis Primers"
                        "fecha" => "2017"
                        "volumen" => "3"
                        "paginaInicial" => "17004"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selumetinib in children with inoperable plexiform neurofibromas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1912735"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2020"
                        "volumen" => "382"
                        "paginaInicial" => "1430"
                        "paginaFinal" => "1442"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lifespan development&#58; symptoms experienced by individuals with neurofibromatosis type 1 associated plexiform neurofibromas from childhood into adulthood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10880-018-9584-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Psychol Med Settings"
                        "fecha" => "2019"
                        "volumen" => "26"
                        "paginaInicial" => "259"
                        "paginaFinal" => "270"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3171/2012.9.JNS101610"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurosurg"
                        "fecha" => "2013"
                        "volumen" => "118"
                        "paginaInicial" => "142"
                        "paginaFinal" => "148"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type 1 revisited"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1542/peds.2007-3204"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatrics"
                        "fecha" => "2009"
                        "volumen" => "123"
                        "paginaInicial" => "124"
                        "paginaFinal" => "133"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malignant peripheral nerve sheath tumours in neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/jmg.39.5.311"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Med Genet"
                        "fecha" => "2002"
                        "volumen" => "39"
                        "paginaInicial" => "311"
                        "paginaFinal" => "314"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Histopathology and clinical outcome of NF1-associated vs&#46; sporadic malignant peripheral nerve sheath tumors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11060-006-9266-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurooncol"
                        "fecha" => "2007"
                        "volumen" => "82"
                        "paginaInicial" => "187"
                        "paginaFinal" => "192"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between benign and malignant peripheral nerve sheath tumors in NF1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/01.wnl.0000168830.79997.13"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2005"
                        "volumen" => "65"
                        "paginaInicial" => "205"
                        "paginaFinal" => "211"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0953620516303624"
                          "estado" => "S300"
                          "issn" => "09536205"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Second malignant neoplasms in children&#58; an update from the Late Effects Study Group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.1985.3.4.532"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "1985"
                        "volumen" => "3"
                        "paginaInicial" => "532"
                        "paginaFinal" => "538"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Postirradiation neurofibrosarcoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1097-0142(19830315)51:6<1028::aid-cncr2820510610>3.0.co;2-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "1983"
                        "volumen" => "51"
                        "paginaInicial" => "1028"
                        "paginaFinal" => "1033"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malignant schwannoma&#8212;clinical characteristics&#44; survival&#44; and response to therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1097-0142(19810515)47:10<2503::aid-cncr2820471033>3.0.co;2-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "1981"
                        "volumen" => "47"
                        "paginaInicial" => "2503"
                        "paginaFinal" => "2509"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malignant peripheral nerve sheath tumors&#46; A clinicopathologic study of 120 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1097-0142(19860515)57:10<2006::aid-cncr2820571022>3.0.co;2-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "1986"
                        "volumen" => "57"
                        "paginaInicial" => "2006"
                        "paginaFinal" => "2021"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malignant peripheral nerve sheath tumor&#58; the clinical spectrum and outcome of treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/01.wnl.0000078813.05925.2c"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2003"
                        "volumen" => "61"
                        "paginaInicial" => "696"
                        "paginaFinal" => "698"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0085253817300054"
                          "estado" => "S300"
                          "issn" => "00852538"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imaging biomarkers for malignant peripheral nerve sheath tumors in neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000008092"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2019"
                        "volumen" => "93"
                        "paginaInicial" => "e1076"
                        "paginaFinal" => "e1084"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First-line chemotherapy for malignant peripheral nerve sheath tumor &#40;MPNST&#41; versus other histological soft tissue sarcoma subtypes and as a prognostic factor for MPNST&#58; an EORTC soft tissue and bone sarcoma group study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdq338"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2011"
                        "volumen" => "22"
                        "paginaInicial" => "207"
                        "paginaFinal" => "214"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plexiform neurofibromas in children with neurofibromatosis type 1&#58; frequency and associated clinical deficits"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jpeds.2011.04.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "2011"
                        "volumen" => "159"
                        "paginaInicial" => "652"
                        "paginaFinal" => "655&#46;e2"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current status and recommendations for imaging in neurofibromatosis type 1&#44; neurofibromatosis type 2&#44; and schwannomatosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00256-019-03290-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Skeletal Radiol"
                        "fecha" => "2020"
                        "volumen" => "49"
                        "paginaInicial" => "199"
                        "paginaFinal" => "219"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Monitoring of plexiform neurofibroma in children and adolescents with neurofibromatosis type 1 by &#91;18 F&#93;FDG-PET imaging&#46; Is it of value in asymptomatic patients&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/pbc.26733"
                      "Revista" => array:3 [
                        "tituloSerie" => "Pediatr Blood Cancer"
                        "fecha" => "2018"
                        "volumen" => "65"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cancer and central nervous system tumor surveillance in pediatric neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-17-0589"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2017"
                        "volumen" => "23"
                        "paginaInicial" => "e46"
                        "paginaFinal" => "e53"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical value of multiparametric whole-body magnetic resonance imaging over whole-spine magnetic resonance imaging in patients with neurofibromatosis type I"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.wneu.2017.09.066"
                      "Revista" => array:7 [
                        "tituloSerie" => "World Neurosurg"
                        "fecha" => "2017"
                        "volumen" => "108"
                        "paginaInicial" => "729"
                        "paginaFinal" => "737"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0261561414001599"
                          "estado" => "S300"
                          "issn" => "02615614"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gliomas presenting after age 10 in individuals with neurofibromatosis type 1 &#40;NF1&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/wnl.59.5.759"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2002"
                        "volumen" => "59"
                        "paginaInicial" => "759"
                        "paginaFinal" => "761"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "von Recklinghausen neurofibromatosis&#46; II&#46; Incidence of optic gliomata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0161-6420(84)34217-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ophthalmology"
                        "fecha" => "1984"
                        "volumen" => "91"
                        "paginaInicial" => "929"
                        "paginaFinal" => "935"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Optic gliomas in children with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0022-3476(89)80137-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "1989"
                        "volumen" => "114"
                        "paginaInicial" => "788"
                        "paginaFinal" => "792"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Implications of new understandings of gliomas in children and adults with NF1&#58; report of a consensus conference"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/neuonc/noaa036"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuro Oncol"
                        "fecha" => "2020"
                        "volumen" => "22"
                        "paginaInicial" => "773"
                        "paginaFinal" => "784"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nonoptic pathway tumors in children with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000009458"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2020"
                        "volumen" => "95"
                        "paginaInicial" => "e1052"
                        "paginaFinal" => "e1059"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent&#44; refractory&#44; or progressive low-grade glioma&#58; a multicentre&#44; phase 2 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1470-2045(19)30277-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Oncol"
                        "fecha" => "2019"
                        "volumen" => "20"
                        "paginaInicial" => "1011"
                        "paginaFinal" => "1022"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Care of adults with neurofibromatosis type 1&#58; a clinical practice resource of the American College of Medical Genetics and Genomics &#40;ACMG&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/gim.2018.28"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2018"
                        "volumen" => "20"
                        "paginaInicial" => "671"
                        "paginaFinal" => "682"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased breast cancer risk in women with neurofibromatosis type 1&#58; a meta-analysis and systematic review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13053-019-0110-z"
                      "Revista" => array:5 [
                        "tituloSerie" => "Hered Cancer Clin Pract"
                        "fecha" => "2019"
                        "volumen" => "17"
                        "paginaInicial" => "12"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis and adenocarcinoma of &#40;male&#41; breast"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "AMA Arch Derm Syphilol"
                        "fecha" => "1953"
                        "volumen" => "68"
                        "paginaInicial" => "359"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type I with breast cancer&#58; not only for women&#33;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1897-4287-12-15"
                      "Revista" => array:5 [
                        "tituloSerie" => "Hered Cancer Clin Pract"
                        "fecha" => "2014"
                        "volumen" => "12"
                        "paginaInicial" => "5"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis with male breast cancer&#8212;risk factor or co-incidence&#63; Report of two rare cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3233/BD-140387"
                      "Revista" => array:6 [
                        "tituloSerie" => "Breast Dis"
                        "fecha" => "2015"
                        "volumen" => "35"
                        "paginaInicial" => "29"
                        "paginaFinal" => "32"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type 1 and male breast cancer&#58; emerging risk factor&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/jscr/rjw138"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Surg Case Rep"
                        "fecha" => "2017"
                        "volumen" => "2017"
                        "paginaInicial" => "rjw138"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Comprehensive Cancer Network&#46; Genetic&#47;familial high-risk assessment&#58; Breast&#44; ovarian&#44; and pancreatic &#40;Version 1&#46;2022&#41;&#46; Plymouth Meeting&#58; NCCN&#59; 2021 &#91;Accessed September 2021&#93;&#46; Available on&#58; <a target="_blank" href="https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf">https&#58;&#47;&#47;www&#46;nccn&#46;org&#47;professionals&#47;physician&#95;gls&#47;pdf&#47;genetics&#95;bop&#46;pdf</a>&#46;"
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Circumstances of discovery of phaeochromocytoma&#58; a retrospective study of 41 consecutive patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1530/eje.0.1500681"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Endocrinol"
                        "fecha" => "2004"
                        "volumen" => "150"
                        "paginaInicial" => "681"
                        "paginaFinal" => "686"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pheochromocytoma and paraganglioma&#58; an endocrine society clinical practice guideline"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2014-1498"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2014"
                        "volumen" => "99"
                        "paginaInicial" => "1915"
                        "paginaFinal" => "1942"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adrenocortical carcinomas and malignant phaeochromocytomas&#58; ESMO-EURACAN Clinical Practice Guidelines for diagnosis&#44; treatment and follow up"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.annonc.2020.08.2099"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2020"
                        "volumen" => "31"
                        "paginaInicial" => "1476"
                        "paginaFinal" => "1490"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multidisciplinary practice guidelines for the diagnosis&#44; genetic counseling and treatment of pheochromocytomas and paragangliomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12094-021-02622-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Transl Oncol"
                        "fecha" => "2021"
                        "volumen" => "23"
                        "paginaInicial" => "1995"
                        "paginaFinal" => "2019"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gastrointestinal stromal tumors in patients with neurofibromatosis 1&#58; a clinicopathologic and molecular genetic study of 45 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.pas.0000176433.81079.bd"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Surg Pathol"
                        "fecha" => "2006"
                        "volumen" => "30"
                        "paginaInicial" => "90"
                        "paginaFinal" => "96"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "NF1-associated gastrointestinal stromal tumors have unique clinical&#44; phenotypic&#44; and genotypic characteristics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.pas.0000159775.77912.15"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Surg Pathol"
                        "fecha" => "2005"
                        "volumen" => "29"
                        "paginaInicial" => "1170"
                        "paginaFinal" => "1176"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gastrointestinal stromal tumours&#58; ESMO-EURACAN Clinical Practice Guidelines for diagnosis&#44; treatment and follow-up"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdy320"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2018"
                        "volumen" => "29"
                        "numero" => "Suppl 4"
                        "paginaInicial" => "iv267"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis and childhood leukaemia&#47;lymphoma&#58; a population-based UKCCSG study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bjc.1994.431"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Cancer"
                        "fecha" => "1994"
                        "volumen" => "70"
                        "paginaInicial" => "969"
                        "paginaFinal" => "972"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imaging evaluation of plexiform neurofibromas in neurofibromatosis type 1&#58; a survey-based assessment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000012437"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2021"
                        "volumen" => "97"
                        "numero" => "7 Suppl 1"
                        "paginaInicial" => "S111"
                        "paginaFinal" => "S119"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/22548874/0000022200000008/v1_202210061413/S225488742200042X/v1_202210061413/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "46200"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/22548874/0000022200000008/v1_202210061413/S225488742200042X/v1_202210061413/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225488742200042X?idApp=WRCEE"
]
Share
Journal Information

Statistics

Follow this link to access the full text of the article

Review
Diagnostic and follow-up protocol for adult patients with neurofibromatosis type 1 in a Spanish reference unit
Protocolo de diagnóstico y seguimiento de pacientes adultos con neurofibromatosis tipo 1 en una unidad de referencia española
I. Solaresa, D. Vinalb, M. Morales-Conejoa,c,d,
Corresponding author
a Unidad de Enfermedades Minoritarias y Errores Congénitos del Metabolismo del Adulto, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre, Madrid, Spain
b Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain
c Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain
d Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain
Read
11
Times
was read the article
3
Total PDF
8
Total HTML
Share statistics
 array:24 [
  "pii" => "S225488742200042X"
  "issn" => "22548874"
  "doi" => "10.1016/j.rceng.2022.02.007"
  "estado" => "S300"
  "fechaPublicacion" => "2022-10-01"
  "aid" => "2016"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
  "copyrightAnyo" => "2022"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "rev"
  "cita" => "Rev Clin Esp. 2022;222:486-95"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0014256522000182"
      "issn" => "00142565"
      "doi" => "10.1016/j.rce.2022.02.001"
      "estado" => "S300"
      "fechaPublicacion" => "2022-10-01"
      "aid" => "2016"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "rev"
      "cita" => "Rev Clin Esp. 2022;222:486-95"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:1 [
        "total" => 0
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">REVISI&#211;N</span>"
        "titulo" => "Protocolo de diagn&#243;stico y seguimiento de pacientes adultos con neurofibromatosis tipo 1 en una unidad de referencia espa&#241;ola"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "486"
            "paginaFinal" => "495"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Diagnostic and follow-up protocol for adult patients with neurofibromatosis type 1 in a Spanish reference unit"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0010"
            "etiqueta" => "Figura 2"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr2.jpeg"
                "Alto" => 1929
                "Ancho" => 2925
                "Tamanyo" => 478317
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Propuesta de abordaje inicial y seguimiento de pacientes con neurofibromatosis tipo 1&#46; G-I&#58; gastrointestinal&#59; GIST&#58; tumor del estroma gastrointestinal&#59; HTA&#58; hipertensi&#243;n arterial&#59; NP&#58; neurofibroma plexiforme&#59; PET&#58; tomograf&#237;a por emisi&#243;n de positrones&#59; RM&#58; resonancia magn&#233;tica&#59; TC&#58; tomograf&#237;a computarizada&#59; TMVNP&#58; tumores malignos de la vaina nerviosa perif&#233;rica&#59; TVNP&#58; tumores de la vaina nerviosa perif&#233;rica&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "I&#46; Solares, D&#46; Vinal, M&#46; Morales-Conejo"
            "autores" => array:3 [
              0 => array:2 [
                "nombre" => "I&#46;"
                "apellidos" => "Solares"
              ]
              1 => array:2 [
                "nombre" => "D&#46;"
                "apellidos" => "Vinal"
              ]
              2 => array:2 [
                "nombre" => "M&#46;"
                "apellidos" => "Morales-Conejo"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S225488742200042X"
          "doi" => "10.1016/j.rceng.2022.02.007"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225488742200042X?idApp=WRCEE"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000182?idApp=WRCEE"
      "url" => "/00142565/0000022200000008/v1_202209290544/S0014256522000182/v1_202209290544/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:20 [
    "pii" => "S2254887422000467"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2022.03.005"
    "estado" => "S300"
    "fechaPublicacion" => "2022-10-01"
    "aid" => "2029"
    "copyright" => "The Authors"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "pgl"
    "cita" => "Rev Clin Esp. 2022;222:496-9"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Consensus Document</span>"
      "titulo" => "Executive summary on the treatment of type 2 diabetes mellitus in elderly or frail individuals&#46; 2022 update of the 2018 consensus document &#8220;Treatment of type 2 diabetes mellitus in the elderly&#8221;"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "496"
          "paginaFinal" => "499"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Resumen ejecutivo sobre el tratamiento de la diabetes mellitus tipo 2 en personas de edad avanzada o fr&#225;giles&#46; Actualizaci&#243;n 2022 del documento de consenso 2018 &#171;Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano&#187;"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 3806
              "Ancho" => 2925
              "Tamanyo" => 687974
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0005"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Strategy for starting and intensifying hypoglycemic treatment and therapy with full insulin regimens&#46; GLP-1ra&#58; GLP-1 receptor agonists&#59; CVD&#58; cardiovascular disease&#59; CKD&#58; chronic kidney disease&#59; FPG&#58; fasting plasma glucose&#59; PPG&#58; preprandial plasma glucose&#59; HF&#58; heart failure&#59; DPP-4i&#58; DPP-4 inhibitors&#59; SGLT-2i&#58; SGLT-2 inhibitors&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "F&#46; G&#243;mez-Peralta, F&#46;J&#46; Carrasco-S&#225;nchez, A&#46; P&#233;rez, J&#46; Escalada, F&#46; &#193;lvarez-Guisasola, C&#46; Miranda-Fern&#225;ndez-Santos, J&#46;J&#46; Mediavilla-Bravo, R&#46; G&#243;mez-Huelgas"
          "autores" => array:8 [
            0 => array:2 [
              "nombre" => "F&#46;"
              "apellidos" => "G&#243;mez-Peralta"
            ]
            1 => array:2 [
              "nombre" => "F&#46;J&#46;"
              "apellidos" => "Carrasco-S&#225;nchez"
            ]
            2 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "P&#233;rez"
            ]
            3 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Escalada"
            ]
            4 => array:2 [
              "nombre" => "F&#46;"
              "apellidos" => "&#193;lvarez-Guisasola"
            ]
            5 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "Miranda-Fern&#225;ndez-Santos"
            ]
            6 => array:2 [
              "nombre" => "J&#46;J&#46;"
              "apellidos" => "Mediavilla-Bravo"
            ]
            7 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "G&#243;mez-Huelgas"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256522000686"
        "doi" => "10.1016/j.rce.2022.03.004"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000686?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887422000467?idApp=WRCEE"
    "url" => "/22548874/0000022200000008/v1_202210061413/S2254887422000467/v1_202210061413/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2254887422000443"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2022.02.009"
    "estado" => "S300"
    "fechaPublicacion" => "2022-10-01"
    "aid" => "2024"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Rev Clin Esp. 2022;222:479-85"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Brief Original</span>"
      "titulo" => "Effect of HCV eradication on critical flicker frequency in HIV&#47;HCV coinfected patients with advanced cirrhosis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "479"
          "paginaFinal" => "485"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Efecto de la erradicaci&#243;n del VHC sobre la frecuencia cr&#237;tica de parpadeo en pacientes coinfectados por VIH&#47;VHC con cirrosis avanzada"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1903
              "Ancho" => 2516
              "Tamanyo" => 379949
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0005"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient flowchart&#46; CFF&#58; critical flicker frequency&#59; SVR&#58; sustained virologic response&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "V&#46; Honta&#241;&#243;n, J&#46; Gonz&#225;lez-Garc&#237;a, R&#46; Rubio-Mart&#237;n, C&#46; D&#237;ez, L&#46; Serrano-Morago, J&#46; Berenguer"
          "autores" => array:7 [
            0 => array:2 [
              "nombre" => "V&#46;"
              "apellidos" => "Honta&#241;&#243;n"
            ]
            1 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Gonz&#225;lez-Garc&#237;a"
            ]
            2 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "Rubio-Mart&#237;n"
            ]
            3 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "D&#237;ez"
            ]
            4 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Serrano-Morago"
            ]
            5 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Berenguer"
            ]
            6 => array:1 [
              "colaborador" => "on behalf of the ESCORIAL Study Group"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256522000261"
        "doi" => "10.1016/j.rce.2022.02.008"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000261?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887422000443?idApp=WRCEE"
    "url" => "/22548874/0000022200000008/v1_202210061413/S2254887422000443/v1_202210061413/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Diagnostic and follow-up protocol for adult patients with neurofibromatosis type 1 in a Spanish reference unit"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "486"
        "paginaFinal" => "495"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "I&#46; Solares, D&#46; Vinal, M&#46; Morales-Conejo"
        "autores" => array:3 [
          0 => array:3 [
            "nombre" => "I&#46;"
            "apellidos" => "Solares"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "D&#46;"
            "apellidos" => "Vinal"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:4 [
            "nombre" => "M&#46;"
            "apellidos" => "Morales-Conejo"
            "email" => array:1 [
              0 => "montserrat.morales@salud.madrid.org"
            ]
            "referencia" => array:4 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              3 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Unidad de Enfermedades Minoritarias y Errores Cong&#233;nitos del Metabolismo del Adulto&#44; Servicio de Medicina Interna&#44; Hospital Universitario 12 de Octubre&#44; Madrid&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Oncolog&#237;a M&#233;dica&#44; Hospital Universitario La Paz&#44; Madrid&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Instituto de Investigaci&#243;n Hospital 12 de Octubre &#40;i&#43;12&#41;&#44; Madrid&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Centro de Investigaci&#243;n Biom&#233;dica en Red de Enfermedades Raras &#40;CIBERER&#41;&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Protocolo de diagn&#243;stico y seguimiento de pacientes adultos con neurofibromatosis tipo 1 en una unidad de referencia espa&#241;ola"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2482
            "Ancho" => 2508
            "Tamanyo" => 527886
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic manifestations in individuals with neurofibromatosis type 1&#46; CNS&#58; central nervous system&#59; GIST&#58; gastrointestinal stromal tumor&#59; PNS&#58; peripheral nervous system&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0040" class="elsevierStylePara elsevierViewall">Neurofibromatosis &#40;NF&#41; is a heterogeneous group of neurocutaneous genetic disorders that are associated with the development of central and peripheral nervous system tumors&#46; There are three subtypes of NF&#58; NF1&#44; NF2&#44; and schwannomatosis<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">NF1 &#40;OMIM <a href="omim:#162200">&#35;162200</a>&#41; is the most prevalent form and represents 96&#37; of all cases&#46; This disease&#44; also known as von Recklinghausen&#8217;s disease&#44; is inherited with an autosomal dominant nature&#46; Its worldwide incidence is around one out of every 3000 individuals<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; NF1 is caused by a pathogenic variant of the NF1 tumor suppressor gene&#44; located on chromosome 17q11&#46;2&#46; In 90&#37; of cases&#44; this mutations leads to loss of function of the NF1 gene product&#44; neurofibromin&#44; which leads to an increase in RAS activity and promotes activation of the signaling cascade of the mitogen-activated protein kinase &#40;MEK&#41;&#47;extracellular signal-regulated kinase pathway&#44; which is frequently involved in the development of cancer<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; For this reason&#44; in addition to presenting with cutaneous&#44; ophthalmic&#44; and bone manifestations&#44; patients affected by NF1 have a high predisposition to developing both benign and malignant tumors including&#44; among others&#44; peripheral nerve sheath tumors&#44; gliomas&#44; breast cancer&#44; pheochromocytomas&#44; and gastrointestinal stromal tumors &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">NF2 and schwannomatosis are rare diseases compared to NF1&#44; representing 3&#37; and &#60;1&#37; of the total number of NF&#44; respectively&#46; NF2 tends to be associated with hypoacusis and vestibular dysfunction&#46; Multiple schwannomas are a distinctive characteristic of schwannomatosis that are habitually associated with intense pain<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In this review&#44; we summarize the diagnosis and main clinical characteristics and propose a screening and follow-up protocol for adult patients with NF1&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Diagnosis of NF1 by clinical criteria and genetic confirmation</span><p id="par0060" class="elsevierStylePara elsevierViewall">In 1988&#44; the clinical criteria for the diagnosis of NF1 were established at the United States of America&#8217;s National Institutes of Health consensus conference &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The gene associated with NF1 was discovered a few years after the publication of said consensus<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; The NF1 gene contains 60 exons and generates multiple isoforms through alternative splicing&#46; More than 1400 mutations in this gene have been described&#44; the majority of which are due to loss-of-function mutations<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Although the identification of NF1 mutations continues to be difficult due to the large size of the gene as well as the great variety of mutations that have been identified&#44; both tools provide benefits in the diagnosis and follow-up of these patients&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">1</span><p id="par0075" class="elsevierStylePara elsevierViewall">The genetic study can help diagnose cases of NF1 in which a clinical diagnosis cannot be established with certainly&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">2</span><p id="par0080" class="elsevierStylePara elsevierViewall">It has been described that certain types of mutations&#44; such as NF1 microdeletions&#44; entail a greater risk of developing malignant neoplasms&#44; thus the identification of these subjects is essential<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">3</span><p id="par0085" class="elsevierStylePara elsevierViewall">Fifty percent of NF1 mutations are <span class="elsevierStyleItalic">de novo</span>&#46; Therefore&#44; in half of the cases&#44; a genetic study in family members could help diagnose other carriers of the defect<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">4</span><p id="par0090" class="elsevierStylePara elsevierViewall">The identification of familial mutation in NF1 will facilitate genetic counseling and the selection of embryos in the case of wanting to become pregnant<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">5</span><p id="par0095" class="elsevierStylePara elsevierViewall">In addition&#44; the absence of a genetic confirmation does not rule out the disease in patients who meet clinical criteria&#44; given that the possibility of an unknown mutation in the NF1 locus or causal mutations in other loci of the genome cannot be ruled out<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46;</p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Cutaneous involvement</span><p id="par0100" class="elsevierStylePara elsevierViewall">Skin manifestations of NF1 are a hallmark of the disease and form part of the diagnostic criteria&#46; They consist of &#8220;caf&#233;-au-lait&#8221; macules&#44; freckling&#44; and neurofibromas&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">&#8220;Caf&#233;-au-lait&#8221; macules are pigmented macules with smooth borders that are chocolate brown in color&#46; They are present in 75&#37; of children and 90&#37; of adolescents and adults<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; These lesions do not pose a risk of malignant transformation&#44; tend to darken with exposure to sunlight&#44; and lighten with age&#46; Neither the size nor the number of &#8220;caf&#233;-au-lait&#8221; macules are directly related to greater disease severity<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">These lesions are present in approximately 10&#37; of the general population as well as in individuals with other genetic syndromes&#44; such as Silver-Russell dwarfism or LEOPARD&#44; Peutz-Jeghers&#44; Legius&#44; Noonan&#44; or McCune-Albright syndromes<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;14</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Freckles are mainly located in intertriginous areas such as the axillas&#44; where they are known as Crowe&#8217;s sign&#44; and the inguinal region&#46; They tend to appear in late childhood or puberty<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Neurofibromas are benign tumors consisting of Schwann cells&#44; perineurial cells&#44; fibroblasts&#44; mast cells&#44; axonal processes&#44; and an extracellular matrix composed of abundant collagen<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; These tumors are observed in almost all adults with NF1&#46; Although there is no risk of malignant transformation&#44; they can cause pruritus and pain as well as cosmetic problems&#46; In fact&#44; it is common for patients with NF1 to describe neurofibromas as the main drawback of their disease&#44; especially in cases in which resection is a challenge due to the numerous lesions they may present with<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to conduct a physical examination with a comprehensive skin evaluation annually&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ophthalmologic involvement</span><p id="par0130" class="elsevierStylePara elsevierViewall">Four main manifestations must be evaluated through ophthalmologic screening in patients with NF1&#58; Lisch nodules&#44; optic pathway gliomas&#44; sphenoid dysplasia&#44; and orbital plexiform neurofibromas &#40;PN&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In most adult patients with NF1&#44; small melanocytic hamartomas can be identified in the iris on a slit lamp examination&#46; These lesions&#44; called Lisch nodules&#44; are characteristic of this disease and do not interfere with vision&#46; They should not be confused with iris nevi&#44; which are common in healthy individuals<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Presence of an optic glioma should be suspected in patients with NF1 who develop unilateral proptosis&#44; visual field defects&#44; strabismus&#44; an afferent pupillary defect&#44; or optic disc edema&#47;atrophy&#46; In addition&#44; tumors with a chiasmatic location may manifest in the form of early puberty<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Around 15&#37; of patients with NF1 develop optic gliomas&#44; but in most cases&#44; they do not cause any clinical repercussions&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Orbital neurofibromas are often accompanied by skull deformities&#46; A skeletal anomaly characteristic of NF1 is the partial or complete absence of the greater wing of the sphenoid bone&#44; with the consequent communication between the medial cranial fossa and the socket&#46; This defect leads to the temporal lobe being able to herniate towards the socket and cause pulsatile exophthalmos or&#44; less often&#44; the orbital content can herniate in the medial cranial fossa and cause enophthalmos<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to conduct a comprehensive ophthalmologic examination &#40;color vision&#44; visual field&#44; ocular motility&#44; pupillary reflexes&#44; slit lamp examination&#44; and fundoscopy&#41; at the time of diagnosis followed by annual exams&#46; Radiological follow-up is only ordered in the case of presenting with indicative symptoms<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Skeletal involvement</span><p id="par0160" class="elsevierStylePara elsevierViewall">Approximately 50&#37; of patients have significant musculoskeletal manifestations&#44; the most common of which are scoliosis and congenital tibial dysplasia&#46; Other bone manifestations include short height&#44; pseudoarthrosis&#44; massive subperiosteal bone proliferation&#44; and intraosseous cystic lesions that can resemble a malignant neoplasm<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; It has also been described that young subjects with NF1 have reduced bone mass&#44; especially in the lumbar spine area&#44; due to the loss of function of neurofibromin&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to follow-up on the bone mineral profile through blood levels of vitamin D and PTH annually together with a densitometric study every three to five years<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Cardiovascular involvement</span><p id="par0170" class="elsevierStylePara elsevierViewall">The term &#8220;NF1 vasculopathy&#8221; has recently been coined to describe the vascular lesions these patients present with&#46; Although the frequency of this type of disease is difficult to define because it is not routinely screened for&#44; its prevalence is estimated to be from 0&#46;4&#37;&#8211;6&#46;4&#37;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46; This entity encompasses aneurysms&#44; stenosis&#44; or malformations of medium- and large-caliber arteries and veins and cardiovascular malformations &#40;pulmonary stenosis and coarctation of the aorta&#41;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#46; Therefore&#44; it is recommendable to order an echocardiogram in the first evaluation of patients with NF1&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Stenosis of the renal artery occurs in approximately 2&#37; of the population with NF1 and its diagnosis must be considered in hypertensive patients or those in whom an abdominal bruit is identified&#46; Although the gold standard for the diagnosis of renal artery stenosis is renal arteriography&#44; the study can be started by means of less invasive tests&#44; such as a Doppler ultrasound or magnetic resonance &#40;MR&#41; angiography<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Pheochromocytoma is an uncommon cause of hypertension&#44; but it occurs in around 2&#37; of adult patients with NF1&#46; Its clinical presentation often includes palpitations&#44; headache&#44; dizziness&#44; or sweating in addition to hypertension<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> Blood pressure must be periodically monitored at home and must be below 140&#47;90&#8239;mmHg or 130&#47;85 in individuals with target organ lesions or diabetes&#46; The presence of hypertension makes it necessary to rule out secondary causes such as renal artery stenosis or the presence of pheochromocytoma&#44; especially in the case of young patients&#44; pregnant women&#44; or elderly individuals with refractory hypertension&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Neuropsychological involvement</span><p id="par0190" class="elsevierStylePara elsevierViewall">Neurocognitive problems are the most common neurological complication in individuals with NF1 and include both an intellectual quotient in the medium-low range and specific cognitive deficits in the areas of attention&#44; executive function&#44; and language skills&#46; A greater frequency of autism spectrum disorders has also been described<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#8211;30</span></a>&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Therefore&#44; in order to increase their possibilities of academic&#44; occupational&#44; and social success as adults&#44; patients with NF1 must be evaluated from an early age by pediatric neuropsychologists&#44; physical therapists&#44; and speech and&#47;or occupational therapists&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">What&#8217;s more&#44; epilepsy is present in approximately 4&#37;&#8211;6&#37; of individuals of NF1 and is commonly related to the development of central nervous system neoplasms or with an underlying cortical dysgenesis<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#46; They often present with partial seizures and it is relatively simple to control with anti-seizure treatment<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Although the risk of dementia in NF1 is little described&#44; recent studies link this entity with a greater predisposition toward the development of cognitive impairment&#44; especially Alzheimer&#8217;s disease<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to perform a brain MR imaging test in all patients with NF1 who present with an initial epileptic seizure and in those with new-onset focal neurological signs&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Oncological involvement</span><p id="par0215" class="elsevierStylePara elsevierViewall">The incidence of cancer in patients with NF1 is five to ten times greater than in the general population&#44; with a cumulative risk of cancer of 40&#37; at 50 years of age<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a>&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Neurofibromas are the most prevalent benign tumors whereas low-grade gliomas and malignant peripheral nerve sheath tumors &#40;MPNST&#41; are the most common malignant neoplasms<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46; Likewise&#44; cancer is the most frequent cause of death in these patients<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#46; MPNST&#44; breast cancer&#44; and high-grade gliomas the most typical manifestations of NF1 in adulthood &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0225" class="elsevierStylePara elsevierViewall">A physical examination and patient education in order to detect warning signs are the fundamental pillars in follow-up&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Plexiform neurofibromas</span><p id="par0230" class="elsevierStylePara elsevierViewall">PN are benign tumors of the peripheral nerve sheath that occur in up to 50&#37; of patients with NF1<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#46; They can be superficial or deep&#46; They tend to be present at birth and grow more notably during the first decade of life<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Despite their benign behavior&#44; they are an important cause of morbidity due to local invasion&#44; including pain&#44; motor dysfunction&#44; and vision loss<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&#46; Furthermore&#44; there is a risk of malignant degeneration to MPNST<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&#46; Symptomatic treatment is surgical but&#44; on many occasions&#44; it is technically complicated<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&#46; In patients with inoperable PN&#44; MEK inhibitors and cabozantinib have demonstrated clinical benefits such as a reduction in tumor size and pain intensity and an improvement in quality of life&#44; with a manageable toxicity profile<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; Selumetinib&#44; a selective MEK inhibitor<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#44; was approved by the Food and Drug Administration in May 2020 for this scenario&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Malignant peripheral nerve sheath tumor</span><p id="par0240" class="elsevierStylePara elsevierViewall">MPNST is an aggressive type of soft tissue sarcoma that is very uncommon in the general population&#44; but observed in 10&#37;&#8211;15&#37; of patients with NF1<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46; In patients with NF1&#44; MPNST occurs almost exclusively on PN&#46; They are locally aggressive neoplasms with a high potential for metastasis&#46; MPNST are one of the principal causes of mortality<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;43</span></a>&#46; The presence of internal PN<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&#44; NF1 locus germline microdeletion<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#44; and prior radiation are risk factors for its onset<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">45&#44;46</span></a>&#46; An MPNST are most often located on the limbs and trunk<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;48</span></a>&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">An MPNST is suspected when there is a brusque change in the pre-existing PN&#44; whether that be an increase in pain&#44; the size of the tumor mass&#44; or progression of neurological impairment<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a>&#46; When there is clinical suspicion&#44; a diffusion-weighted MR imaging test and&#47;or a PET-computed tomography &#40;CT&#41; scan must be performed<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&#46; The definitive diagnosis of MPNST requires histological confirmation&#46; Treatment of MPNST must be performed by a multidisciplinary team in centers with experience in soft tissue sarcomas<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a>&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation&#58;</span> There is no consensus on screening asymptomatic patients with NF1<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a>&#46; Therefore&#44; some reference centers have established their own screening protocols with whole-body diffusion-weighted MR imaging tests or PET-CT scans in patients at &#8220;high risk&#8221; for malignant transformation&#46; Some clinical guidelines<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> recommend performing whole-body MR imaging in patients between 16&#8211;20 years of age before their transition to the adult unit in order to establish the baseline internal PN burden&#44; given that somatic growth may have ended by that time<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">53&#8211;55</span></a>&#46; This management requires prospective validation&#46; In centers where whole-body MR imaging is not available&#44; performing a brain and neuroaxis MR imaging could be considered<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Brain tumors</span><p id="par0255" class="elsevierStylePara elsevierViewall">Central nervous system tumors as a whole are the most common neoplasms in patients with NF1<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a> and represent one of the most habitual causes of mortality<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">The most common tumors are optic nerve gliomas&#44; which are usually low-grade pilocytic astrocytomas&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> They occur in 15&#37; of children younger than six years of age and are exceptional after adolescence<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a>&#46; They may entail a decrease in visual acuity&#44; abnormalities in discerning colors&#44; abnormal pupillary function&#44; and proptosis<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a>&#46; The gold standard for diagnosis is MR imaging&#44; although optical coherence tomography has shown promising results&#46; The initial treatment tends to include an observation period&#44; if possible&#46; If there is progression&#44; treatment with chemotherapy or surgery is considered&#46; Radiotherapy tends to be avoided due to the risk of secondary tumors<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Patients with NF1 also tend to be at greater risk of developing low-grade astrocytomas in other locations &#40;5&#37;&#41;&#44; included the basal ganglia&#44; cerebellum&#44; or brain stem&#44; as well as high-grade gliomas &#40;1&#37;&#8211;2&#37;&#41; at younger ages<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46; The most common clinical presentation is an increase in intracranial pressure&#44; although they tend to be asymptomatic<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a>&#46; The treatment is similar to that of patients without NF1<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&#46; Treatment with MEK inhibitors such as selumetinib&#44; trametinib&#44; and binimetinib is showing promising results<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a>&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> It is recommended to screen for optic nerve gliomas by means of ophthalmologic examinations every six or 12 months until eight years of age &#40;the age of greatest risk&#41; and then every two years until 18 years of age&#44; after which its onset is extremely rare<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;60</span></a>&#46; Screening for other low-grade astrocytomas is not routinely performed&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Breast cancer in patients with NF1</span><p id="par0275" class="elsevierStylePara elsevierViewall">Women with NF1 have a greater risk of developing breast cancer and at an earlier age than the general population<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35&#44;63&#44;64</span></a>&#46; Women younger than 50 years with NF1 have a five-fold risk of developing breast cancer&#44; present with more advanced stage cancer upon diagnosis&#44; and have greater mortality<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;64</span></a>&#46; The risk of breast cancer in men with NF1 appears to be low<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">65&#8211;68</span></a>&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation&#58;</span> Clinical guidelines<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">63&#44;69</span></a> recommend screening for breast cancer starting at 30 years of age and consider a breast MR imaging test with contrast between 30 and 50 years of age&#46; Screening can begin earlier according to family history&#44; starting it five to ten years before the earliest age of breast cancer diagnosis in the family<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">63&#44;69</span></a>&#46; It is important to highlight the risk of false positives on imaging tests and their difficult interpretation due to the presence of mammary neurofibromas<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a>&#46; At present&#44; there is not enough evidence to recommend a radical mastectomy&#44; although it could be considered based on family history<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Pheochromocytomas</span><p id="par0285" class="elsevierStylePara elsevierViewall">Pheochromocytomas are catecholamine-secreting tumors which emerge on the chromaffin cells of the adrenal medulla&#46; They are rare in the general population&#44; but their incidence increases in patients with NF1<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&#46; They are diagnosed in the fourth decade of life and their location tends to be adrenal<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">The most typical clinical manifestation is the classic triad of paroxysmal episodes of headache&#44; sweating&#44; and tachycardia&#46; However&#44; the most common symptom that tends to lead to a diagnosis is new-onset hypertension<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a>&#46; When faced with these symptoms&#44; a 24-h urinary fractionated metanephrines test or a plasma free metanephrines and methoxytyramine test should be ordered<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a>&#46; In case of biochemical confirmation&#44; an abdominal CT scan or MR imaging test will be performed&#46; For more information on diagnosis and treatment&#44; specific clinical guidelines should be consulted<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">72&#44;73</span></a>&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation and follow-up&#58;</span> Given the lack of randomized studies on the efficacy of biochemical or imaging test screening for detecting pheochromocytomas in asymptomatic patients with NF1&#44; the main clinical guidelines do not recommend it&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Gastrointestinal stromal tumors</span><p id="par0300" class="elsevierStylePara elsevierViewall">Gastrointestinal stromal tumors are uncommon mesenchymal neoplasms of the gastrointestinal tract which&#44; despite their low frequency in patients with NF1 &#40;0&#46;2&#37;&#8211;1&#46;2&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a>&#44; are more common than in the general population &#40;standardized incidence ratio &#40;SIR&#41;&#58; 51&#46;2&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#41;&#46; In patients with NF1&#44; they are predominantly located in the small intestine &#40;65&#37; in the jejunum and ileum&#41;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a>&#46; Somatic mutations in KIT or PDGFRA are rare&#44; unlike sporadic cases<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">74&#44;75</span></a>&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">The most common clinical manifestations tend to be gastrointestinal bleeding or anemia&#46; The diagnosis is made by means of a CT scan with contrast and a biopsy&#44; when possible&#46; Treatment is surgical&#44; except in metastatic disease&#46; In that scenario&#44; kinase-tyrosine inhibitors have been demonstrated to prolong survival<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a>&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation&#58;</span> There are currently no randomized studies which justify screening in asymptomatic patients with NF1&#44; but performing an abdominal or thoracic-abdominal-pelvic CT scan with contrast is recommended when there is clinical suspicion<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a>&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Other tumors</span><p id="par0315" class="elsevierStylePara elsevierViewall">Other characteristic malignant neoplasms in patients with NF1 in pediatric ages are embryonal rhabdomyosarcoma<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#44; with a mean age of onset of two years&#44; and myelomonocytic leukemia<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a>&#46; Patients with NF1 are at increased risk of developing other tumors at earlier ages and with a worse prognosis compared to the general population&#46; Of note among them are undifferentiated pleomorphic sarcoma &#40;odds ratio &#40;OR&#41;&#58; 23&#41; and other sarcomas&#44; melanoma &#40;OR&#58; 3&#46;9&#41;&#44; and ovarian cancer &#40;OR&#58; 5&#46;6&#41;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proposal for evaluation&#58;</span> There is currently no evidence to recommend biochemical or radiological screening for other tumors&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Algorithm for transfer to the adult unit and recommendations for follow-up</span><p id="par0325" class="elsevierStylePara elsevierViewall">Our proposal for the management of adult patients with NF1 is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; Transferring patients with NF1 to the adult rare disease unit at 16&#8211;18 years of age is proposed&#46; A neuropsychiatric and ophthalmic evaluation will be conducted both if it has not been performed in these patients before and in those diagnosed in adult ages&#46; Genetic counseling will be provided to all recently diagnosed patients and at the time they wish to become pregnant&#46; A baseline echocardiogram and MR imaging test of the skull will be ordered&#46; Optionally&#44; a whole-body MR imaging test can be requested in order to establish the baseline internal neurofibroma burden&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0330" class="elsevierStylePara elsevierViewall">Annual follow-up that includes a skin evaluation&#44; blood pressure monitoring&#44; and a neurological and ophthalmologic examination is proposed&#46; An annual blood test will be performed to evaluate vitamin D levels and a densitometric scan will be performed every three to five years&#46; An annual mammogram will be performed in women starting at 30 years of age&#46; In patients at high risk for malignant transformation of PN&#44; a periodic whole-body MR imaging test or PET-CT scan should be evaluated&#46; There is currently no consensus among specialists or robust prospective evidence on the utility of imaging screening and the type of test that should be performed in asymptomatic patients&#46; The suitability of a whole-body MR imaging as a screening method and the periodicity with which it should be performed in high-risk patients is currently under study<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">78</span></a>&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">In each consultation&#44; focus will be placed on warning signs such as blood pressure&#59; neurological abnormalities&#59; psychiatric abnormalities&#59; and changes in pain&#44; size&#44; or progression of neurological impairment in previous neurofibromas&#46; When alarm signs or symptoms are detected&#44; action will be taken in accordance with the algorithm shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; This algorithm is based on the main clinical guidelines for the management of patients with NF1<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;14&#44;27&#44;53</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;60&#44;63</span></a>&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusions</span><p id="par0340" class="elsevierStylePara elsevierViewall">NF1 is a disease that has multisystemic involvement which entails significant morbidity and mortality&#46; In these patients&#44; it is essential to provide adequate genetic counseling&#59; ensure the early detection of possible neuropsychological&#44; cardiovascular&#44; and oncological complications&#44; among others&#59; and offer a specific therapeutic approach in centers with experience in this disease&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0345" class="elsevierStylePara elsevierViewall">This research has not received specific grants from agencies in the public&#44; commercial&#44; or non-profit sectors&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interest</span><p id="par0350" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:17 [
        0 => array:3 [
          "identificador" => "xres1778589"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1561541"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1778590"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1561540"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Diagnosis of NF1 by clinical criteria and genetic confirmation"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Cutaneous involvement"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Ophthalmologic involvement"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Skeletal involvement"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Cardiovascular involvement"
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Neuropsychological involvement"
        ]
        11 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Oncological involvement"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Plexiform neurofibromas"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Malignant peripheral nerve sheath tumor"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Brain tumors"
            ]
            3 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Breast cancer in patients with NF1"
            ]
            4 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Pheochromocytomas"
            ]
            5 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Gastrointestinal stromal tumors"
            ]
            6 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Other tumors"
            ]
          ]
        ]
        12 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Algorithm for transfer to the adult unit and recommendations for follow-up"
        ]
        13 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conclusions"
        ]
        14 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Funding"
        ]
        15 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conflicts of interest"
        ]
        16 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2021-10-14"
    "fechaAceptado" => "2022-02-07"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1561541"
          "palabras" => array:3 [
            0 => "Neurofibromatosis"
            1 => "Plexiform neurofibroma"
            2 => "<span class="elsevierStyleItalic">Caf&#233;-au-lait</span> spots"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1561540"
          "palabras" => array:3 [
            0 => "Neurofibromatosis"
            1 => "Neurofibroma plexiforme"
            2 => "Manchas &#171;caf&#233; con leche&#187;"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Neurofibromatosis type 1 &#40;NF1&#41; is one of the most common genetic neurocutaneous disorders&#46; The hallmark of this disease is skin lesions in the form of caf&#233;-au-lait spots&#44; ephelides&#44; and the characteristic cutaneous neurofibromas&#46; Other common manifestations include bone abnormalities&#44; &#8220;NF1 vasculopathy&#44;&#8221; and neurocognitive disorders&#46; In addition&#44; patients are at an increased risk for a wide variety of malignant neoplasms&#44; including the malignant transformation of plexiform neurofibromas&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">It is necessary to know the various clinical characteristics of this disorder and to provide an early&#44; multidisciplinary follow-up and treatment approach in order to provide optimal care to these patients&#44; who present with a multisystemic disease that is potentially severe&#46; This review summarizes the diagnosis and main clinical characteristics and suggests a protocol for screening and follow-up of adult patients with NF1&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La neurofibromatosis tipo 1 &#40;NF1&#41; es uno de los trastornos gen&#233;ticos neurocut&#225;neos m&#225;s frecuentes&#46; La caracter&#237;stica de esta enfermedad es la afectaci&#243;n cut&#225;nea en forma de manchas caf&#233; con leche&#44; ef&#233;lides y los caracter&#237;sticos neurofibromas cut&#225;neos&#46; Otras manifestaciones frecuentes incluyen las alteraciones &#243;seas&#44; la &#171;vasculopat&#237;a por NF1&#187; y los problemas neurocognitivos&#46; Adem&#225;s&#44; los pacientes tienen m&#225;s riesgo de padecer una gran variedad de neoplasias malignas&#44; incluida la transformaci&#243;n maligna de neurofibromas plexiformes&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Para ser capaces de brindar una atenci&#243;n &#243;ptima a estos pacientes&#44; que presentan una afectaci&#243;n multisist&#233;mica y potencialmente grave&#44; es necesario conocer las diversas caracter&#237;sticas cl&#237;nicas de este trastorno&#44; as&#237; como propiciar un seguimiento y abordaje terap&#233;utico precoz y multidisciplinar&#46; En esta revisi&#243;n&#44; resumimos el diagn&#243;stico&#44; las principales caracter&#237;sticas cl&#237;nicas y proponemos un protocolo de cribado y seguimiento de pacientes adultos con NF1&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Solares I&#44; Vinal D&#44; Morales-Conejo M&#46; Protocolo de diagn&#243;stico y seguimiento de pacientes adultos con neurofibromatosis tipo 1 en una unidad de referencia espa&#241;ola&#46; Rev Clin Esp&#46; 2022&#59;222&#58;486&#8211;495&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2482
            "Ancho" => 2508
            "Tamanyo" => 527886
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic manifestations in individuals with neurofibromatosis type 1&#46; CNS&#58; central nervous system&#59; GIST&#58; gastrointestinal stromal tumor&#59; PNS&#58; peripheral nervous system&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1929
            "Ancho" => 2925
            "Tamanyo" => 516944
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Proposal for the initial approach and follow-up on patients with neurofibromatosis type 1&#46; G-I&#58; gastrointestinal&#59; GIST&#58; gastrointestinal stromal tumor&#59; HT&#58; hypertension&#59; PN&#58; plexiform neurofibroma&#59; PET&#58; positron emission tomography&#59; MR&#58; magnetic resonance&#59; CT&#58; computed tomography&#59; MPNST&#58; malignant peripheral nerve sheath tumor&#59; PNST&#58; peripheral nerve sheath tumor&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">NF1&#58; neurofibromatosis type 1&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Two or more of the following clinical characteristics are enough to establish a diagnosis of neurofibromatosis type 1&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0005" class="elsevierStylePara elsevierViewall">Six or more &#8220;caf&#233;-au-lait&#8221; macules with a diameter greater than 5&#8239;mm in prepubescent subjects or 15&#8239;mm in postpubescent subjects</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0010" class="elsevierStylePara elsevierViewall">Two or more neurofibromas of any type or a plexiform neurofibroma</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0015" class="elsevierStylePara elsevierViewall">Freckling in the axillary or inguinal region</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0020" class="elsevierStylePara elsevierViewall">Optic nerve glioma</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0025" class="elsevierStylePara elsevierViewall">Two or more Lisch nodules &#40;iris hamartomas&#41;</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">A distinctive bone lesion such as sphenoid dysplasia or cortical bone thinning with or without pseudoarthrosis</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">An immediate family member &#40;parents&#44; siblings&#44; or children&#41; with NF1 according to the above criteria</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#8220;Classic&#8221; diagnostic criteria for neurofibromatosis type 1 from the United States of America&#8217;s National Institute of Health&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">MPNST&#58; malignant peripheral nerve sheath tumor&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Birth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Childhood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adolescence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adult age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8220;Caf&#233;-au-lait&#8221; macules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Learning delays&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Freckling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MPNST&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Orbital dysplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Motor or speech delay&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lisch nodules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Breast cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tibial dysplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Attention deficit disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Scoliosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">High-grade glioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pseudoarthrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autism spectrum disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cutaneous neurofibromas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Plexiform neurofibromas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Optic nerve glioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paraspinal neurofibromas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brainstem glioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Development of clinical characteristics in patients with neurofibromatosis type 1&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:78 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis&#58; a review of NF1&#44; NF2&#44; and schwannomatosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;L&#46; Kresak"
                            1 => "M&#46; Walsh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1055/s-0036-1579766"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr Genet"
                        "fecha" => "2016"
                        "volumen" => "5"
                        "paginaInicial" => "98"
                        "paginaFinal" => "104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27617150"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Birth incidence and prevalence of tumor-prone syndromes&#58; estimates from a UK family genetic register service"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;G&#46; Evans"
                            1 => "E&#46; Howard"
                            2 => "C&#46; Giblin"
                            3 => "T&#46; Clancy"
                            4 => "H&#46; Spencer"
                            5 => "S&#46;M&#46; Huson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ajmg.a.33139"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med Genet A"
                        "fecha" => "2010"
                        "volumen" => "152A"
                        "paginaInicial" => "327"
                        "paginaFinal" => "332"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20082463"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas&#58; a comprehensive review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I&#46; Solares"
                            1 => "D&#46; Vi&#241;al"
                            2 => "M&#46; Morales-Conejo"
                            3 => "N&#46; Rodriguez-Salas"
                            4 => "J&#46; Feliu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.esmoop.2021.100223"
                      "Revista" => array:5 [
                        "tituloSerie" => "ESMO Open"
                        "fecha" => "2021"
                        "volumen" => "6"
                        "paginaInicial" => "100223"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34388689"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type 1&#58; a multidisciplinary approach to care"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;C&#46; Hirbe"
                            1 => "D&#46;H&#46; Gutmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1474-4422(14)70063-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Neurol"
                        "fecha" => "2014"
                        "volumen" => "13"
                        "paginaInicial" => "834"
                        "paginaFinal" => "843"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25030515"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current understanding of neurofibromatosis type 1&#44; 2&#44; and schwannomatosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Tamura"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/ijms22115850"
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Mol Sci"
                        "fecha" => "2021"
                        "volumen" => "22"
                        "paginaInicial" => "5850"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34072574"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Neurofibromatosis&#46; Conference statement&#46; National Institutes of Health Consensus Development Conference"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Neurol"
                        "fecha" => "1988"
                        "volumen" => "45"
                        "paginaInicial" => "575"
                        "paginaFinal" => "578"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3128965"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Viskochil"
                            1 => "A&#46;M&#46; Buchberg"
                            2 => "G&#46; Xu"
                            3 => "R&#46;M&#46; Cawthon"
                            4 => "J&#46; Stevens"
                            5 => "R&#46;K&#46; Wolff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0092-8674(90)90252-a"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "1990"
                        "volumen" => "62"
                        "paginaInicial" => "187"
                        "paginaFinal" => "192"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1694727"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A RASopathy gene commonly mutated in cancer&#58; the neurofibromatosis type 1 tumour suppressor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "N&#46; Ratner"
                            1 => "S&#46;J&#46; Miller"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrc3911"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Cancer"
                        "fecha" => "2015"
                        "volumen" => "15"
                        "paginaInicial" => "290"
                        "paginaFinal" => "301"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25877329"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated risk for MPNST in NF1 microdeletion patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; De Raedt"
                            1 => "H&#46; Brems"
                            2 => "P&#46; Wolkenstein"
                            3 => "D&#46; Vidaud"
                            4 => "S&#46; Pilotti"
                            5 => "F&#46; Perrone"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/374821"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2003"
                        "volumen" => "72"
                        "paginaInicial" => "1288"
                        "paginaFinal" => "1292"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12660952"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;E&#46; Ferner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.ejhg.5201676"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Hum Genet"
                        "fecha" => "2007"
                        "volumen" => "15"
                        "paginaInicial" => "131"
                        "paginaFinal" => "138"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16957683"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is it time to change the neurofibromatosis 1 diagnostic criteria&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46; Tadini"
                            1 => "D&#46; Milani"
                            2 => "F&#46; Menni"
                            3 => "L&#46; Pezzani"
                            4 => "C&#46; Sabatini"
                            5 => "S&#46; Esposito"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejim.2014.04.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Intern Med"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "506"
                        "paginaFinal" => "510"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24784952"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Type I neurofibromatosis&#58; case report and review of the literature focused on oral and cutaneous lesions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Buchholzer"
                            1 => "R&#46; Verdeja"
                            2 => "T&#46; Lombardi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/dermatopathology8010003"
                      "Revista" => array:5 [
                        "tituloSerie" => "Dermatopathology &#40;Basel&#41;"
                        "fecha" => "2021"
                        "volumen" => "8"
                        "paginaInicial" => "17"
                        "paginaFinal" => "24"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pathoetiology of neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "E&#46;M&#46; Jouhilahti"
                            1 => "S&#46; Peltonen"
                            2 => "A&#46;M&#46; Heape"
                            3 => "J&#46; Peltonen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajpath.2010.12.056"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Pathol"
                        "fecha" => "2011"
                        "volumen" => "178"
                        "paginaInicial" => "1932"
                        "paginaFinal" => "1939"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21457932"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines for the diagnosis and management of individuals with neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;E&#46; Ferner"
                            1 => "S&#46;M&#46; Huson"
                            2 => "N&#46; Thomas"
                            3 => "C&#46; Moss"
                            4 => "H&#46; Willshaw"
                            5 => "D&#46;G&#46; Evans"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/jmg.2006.045906"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Med Genet"
                        "fecha" => "2007"
                        "volumen" => "44"
                        "paginaInicial" => "81"
                        "paginaFinal" => "88"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17105749"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis 1&#58; clinical manifestations and diagnostic criteria"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;M&#46; Friedman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/088307380201700802"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Child Neurol"
                        "fecha" => "2002"
                        "volumen" => "17"
                        "paginaInicial" => "548"
                        "paginaFinal" => "651"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12403552"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The development of cutaneous neurofibromas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;M&#46; Jouhilahti"
                            1 => "S&#46; Peltonen"
                            2 => "T&#46; Callens"
                            3 => "E&#46; Jokinen"
                            4 => "A&#46;M&#46; Heape"
                            5 => "L&#46; Messiaen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajpath.2010.10.041"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Pathol"
                        "fecha" => "2011"
                        "volumen" => "178"
                        "paginaInicial" => "500"
                        "paginaFinal" => "505"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21281783"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cutaneous neurofibromas in the genomics era&#58; current understanding and open questions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;J&#46; Allaway"
                            1 => "S&#46;J&#46;C&#46; Gosline"
                            2 => "S&#46; La Rosa"
                            3 => "P&#46; Knight"
                            4 => "A&#46; Bakker"
                            5 => "J&#46; Guinney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41416-018-0073-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Cancer"
                        "fecha" => "2018"
                        "volumen" => "118"
                        "paginaInicial" => "1539"
                        "paginaFinal" => "1548"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29695767"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ophthalmological assessment of children with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Cassiman"
                            1 => "E&#46; Legius"
                            2 => "W&#46; Spileers"
                            3 => "I&#46; Casteels"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00431-013-2035-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Pediatr"
                        "fecha" => "2013"
                        "volumen" => "172"
                        "paginaInicial" => "1327"
                        "paginaFinal" => "1333"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23708214"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Orbitotemporal neurofibromatosis&#58; classification and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;H&#46; Erb"
                            1 => "N&#46; Uzcategui"
                            2 => "R&#46;F&#46; See"
                            3 => "M&#46;A&#46; Burnstine"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/01676830600987227"
                      "Revista" => array:6 [
                        "tituloSerie" => "Orbit"
                        "fecha" => "2007"
                        "volumen" => "26"
                        "paginaInicial" => "223"
                        "paginaFinal" => "228"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18097958"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Optic pathway gliomas in children with neurofibromatosis 1&#58; consensus statement from the NF1 Optic Pathway Glioma Task Force"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46; Listernick"
                            1 => "D&#46;N&#46; Louis"
                            2 => "R&#46;J&#46; Packer"
                            3 => "D&#46;H&#46; Gutmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ana.410410204"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Neurol"
                        "fecha" => "1997"
                        "volumen" => "41"
                        "paginaInicial" => "143"
                        "paginaFinal" => "149"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9029062"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Orthopaedic manifestations of neurofibromatosis in children&#58; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;G&#46; Vitale"
                            1 => "A&#46; Guha"
                            2 => "D&#46;L&#46; Skaggs"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00003086-200208000-00013"
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Orthop Relat Res"
                        "fecha" => "2002"
                        "paginaInicial" => "107"
                        "paginaFinal" => "118"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20676810"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Generalized metabolic bone disease in neurofibromatosis type I"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Brunetti-Pierri"
                             …5
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ymgme.2007.12.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Genet Metab"
                        "fecha" => "2008"
                        "volumen" => "94"
                        "paginaInicial" => "105"
                        "paginaFinal" => "111"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vascular abnormalities in patients with neurofibromatosis syndrome type I&#58; clinical spectrum&#44; management&#44; and results"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jvs.2007.03.055"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Vasc Surg"
                        "fecha" => "2007"
                        "volumen" => "46"
                        "paginaInicial" => "475"
                        "paginaFinal" => "484"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1096-8628(20001113)95:2<108::aid-ajmg4>3.0.co;2-0"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Med Genet"
                        "fecha" => "2000"
                        "volumen" => "95"
                        "paginaInicial" => "108"
                        "paginaFinal" => "117"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0085253815302027"
                          "estado" => "S300"
                          "issn" => "00852538"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.106.174526"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2006"
                        "volumen" => "113"
                        "paginaInicial" => "e463"
                        "paginaFinal" => "e654"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of renal vascular disease in neurofibromatosis type 1 and the role of percutaneous transluminal angioplasty"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/17.7.1235"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2002"
                        "volumen" => "17"
                        "paginaInicial" => "1235"
                        "paginaFinal" => "1240"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular disease in neurofibromatosis 1&#58; report of the NF1 Cardiovascular Task Force"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00125817-200205000-00002"
                      "Revista" => array:7 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2002"
                        "volumen" => "4"
                        "paginaInicial" => "105"
                        "paginaFinal" => "111"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0016508508016065"
                          "estado" => "S300"
                          "issn" => "00165085"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Behaviour in children with neurofibromatosis type 1&#58; cognition&#44; executive function&#44; attention&#44; emotion&#44; and social competence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1469-8749.2012.04399.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dev Med Child Neurol"
                        "fecha" => "2013"
                        "volumen" => "55"
                        "paginaInicial" => "111"
                        "paginaFinal" => "125"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The nature and frequency of cognitive deficits in children with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/01.wnl.0000179303.72345.ce"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2005"
                        "volumen" => "65"
                        "paginaInicial" => "1037"
                        "paginaFinal" => "1044"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selective impairment of the executive attentional network in adult patients with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/WNR.0000000000001275"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuroreport"
                        "fecha" => "2019"
                        "volumen" => "30"
                        "paginaInicial" => "921"
                        "paginaFinal" => "926"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epilepsy in neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/08830738030180050501"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Child Neurol"
                        "fecha" => "2003"
                        "volumen" => "18"
                        "paginaInicial" => "338"
                        "paginaFinal" => "342"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epilepsy in individuals with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/epi.12348"
                      "Revista" => array:6 [
                        "tituloSerie" => "Epilepsia"
                        "fecha" => "2013"
                        "volumen" => "54"
                        "paginaInicial" => "1810"
                        "paginaFinal" => "1814"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased risk for dementia in neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41436-021-01261-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2021"
                        "volumen" => "23"
                        "paginaInicial" => "2219"
                        "paginaFinal" => "2222"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Distinctive cancer associations in patients with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2015.65.3576"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2016"
                        "volumen" => "34"
                        "paginaInicial" => "1978"
                        "paginaFinal" => "1986"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of cancer prevalence in patients with neurofibromatosis type 1 at an academic cancer center vs&#46; in the general population from 1985 to 2020"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamanetworkopen.2021.0945"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA Netw Open"
                        "fecha" => "2021"
                        "volumen" => "4"
                        "paginaInicial" => "e210945"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0085253815303598"
                          "estado" => "S300"
                          "issn" => "00852538"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality in neurofibromatosis 1&#58; in North West England&#58; an assessment of actuarial survival in a region of the UK since 1989"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ejhg.2011.113"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Hum Genet"
                        "fecha" => "2011"
                        "volumen" => "19"
                        "paginaInicial" => "1187"
                        "paginaFinal" => "1191"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrdp.2017.4"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Rev Dis Primers"
                        "fecha" => "2017"
                        "volumen" => "3"
                        "paginaInicial" => "17004"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selumetinib in children with inoperable plexiform neurofibromas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1912735"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2020"
                        "volumen" => "382"
                        "paginaInicial" => "1430"
                        "paginaFinal" => "1442"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lifespan development&#58; symptoms experienced by individuals with neurofibromatosis type 1 associated plexiform neurofibromas from childhood into adulthood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10880-018-9584-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Psychol Med Settings"
                        "fecha" => "2019"
                        "volumen" => "26"
                        "paginaInicial" => "259"
                        "paginaFinal" => "270"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3171/2012.9.JNS101610"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurosurg"
                        "fecha" => "2013"
                        "volumen" => "118"
                        "paginaInicial" => "142"
                        "paginaFinal" => "148"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type 1 revisited"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1542/peds.2007-3204"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatrics"
                        "fecha" => "2009"
                        "volumen" => "123"
                        "paginaInicial" => "124"
                        "paginaFinal" => "133"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malignant peripheral nerve sheath tumours in neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/jmg.39.5.311"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Med Genet"
                        "fecha" => "2002"
                        "volumen" => "39"
                        "paginaInicial" => "311"
                        "paginaFinal" => "314"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Histopathology and clinical outcome of NF1-associated vs&#46; sporadic malignant peripheral nerve sheath tumors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11060-006-9266-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurooncol"
                        "fecha" => "2007"
                        "volumen" => "82"
                        "paginaInicial" => "187"
                        "paginaFinal" => "192"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between benign and malignant peripheral nerve sheath tumors in NF1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/01.wnl.0000168830.79997.13"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2005"
                        "volumen" => "65"
                        "paginaInicial" => "205"
                        "paginaFinal" => "211"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0953620516303624"
                          "estado" => "S300"
                          "issn" => "09536205"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Second malignant neoplasms in children&#58; an update from the Late Effects Study Group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.1985.3.4.532"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "1985"
                        "volumen" => "3"
                        "paginaInicial" => "532"
                        "paginaFinal" => "538"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Postirradiation neurofibrosarcoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1097-0142(19830315)51:6<1028::aid-cncr2820510610>3.0.co;2-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "1983"
                        "volumen" => "51"
                        "paginaInicial" => "1028"
                        "paginaFinal" => "1033"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malignant schwannoma&#8212;clinical characteristics&#44; survival&#44; and response to therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1097-0142(19810515)47:10<2503::aid-cncr2820471033>3.0.co;2-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "1981"
                        "volumen" => "47"
                        "paginaInicial" => "2503"
                        "paginaFinal" => "2509"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malignant peripheral nerve sheath tumors&#46; A clinicopathologic study of 120 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/1097-0142(19860515)57:10<2006::aid-cncr2820571022>3.0.co;2-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "1986"
                        "volumen" => "57"
                        "paginaInicial" => "2006"
                        "paginaFinal" => "2021"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malignant peripheral nerve sheath tumor&#58; the clinical spectrum and outcome of treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/01.wnl.0000078813.05925.2c"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2003"
                        "volumen" => "61"
                        "paginaInicial" => "696"
                        "paginaFinal" => "698"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0085253817300054"
                          "estado" => "S300"
                          "issn" => "00852538"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imaging biomarkers for malignant peripheral nerve sheath tumors in neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000008092"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2019"
                        "volumen" => "93"
                        "paginaInicial" => "e1076"
                        "paginaFinal" => "e1084"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First-line chemotherapy for malignant peripheral nerve sheath tumor &#40;MPNST&#41; versus other histological soft tissue sarcoma subtypes and as a prognostic factor for MPNST&#58; an EORTC soft tissue and bone sarcoma group study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdq338"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2011"
                        "volumen" => "22"
                        "paginaInicial" => "207"
                        "paginaFinal" => "214"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plexiform neurofibromas in children with neurofibromatosis type 1&#58; frequency and associated clinical deficits"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jpeds.2011.04.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "2011"
                        "volumen" => "159"
                        "paginaInicial" => "652"
                        "paginaFinal" => "655&#46;e2"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current status and recommendations for imaging in neurofibromatosis type 1&#44; neurofibromatosis type 2&#44; and schwannomatosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00256-019-03290-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Skeletal Radiol"
                        "fecha" => "2020"
                        "volumen" => "49"
                        "paginaInicial" => "199"
                        "paginaFinal" => "219"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Monitoring of plexiform neurofibroma in children and adolescents with neurofibromatosis type 1 by &#91;18 F&#93;FDG-PET imaging&#46; Is it of value in asymptomatic patients&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/pbc.26733"
                      "Revista" => array:3 [
                        "tituloSerie" => "Pediatr Blood Cancer"
                        "fecha" => "2018"
                        "volumen" => "65"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cancer and central nervous system tumor surveillance in pediatric neurofibromatosis 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-17-0589"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2017"
                        "volumen" => "23"
                        "paginaInicial" => "e46"
                        "paginaFinal" => "e53"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical value of multiparametric whole-body magnetic resonance imaging over whole-spine magnetic resonance imaging in patients with neurofibromatosis type I"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.wneu.2017.09.066"
                      "Revista" => array:7 [
                        "tituloSerie" => "World Neurosurg"
                        "fecha" => "2017"
                        "volumen" => "108"
                        "paginaInicial" => "729"
                        "paginaFinal" => "737"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0261561414001599"
                          "estado" => "S300"
                          "issn" => "02615614"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gliomas presenting after age 10 in individuals with neurofibromatosis type 1 &#40;NF1&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/wnl.59.5.759"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2002"
                        "volumen" => "59"
                        "paginaInicial" => "759"
                        "paginaFinal" => "761"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "von Recklinghausen neurofibromatosis&#46; II&#46; Incidence of optic gliomata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0161-6420(84)34217-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ophthalmology"
                        "fecha" => "1984"
                        "volumen" => "91"
                        "paginaInicial" => "929"
                        "paginaFinal" => "935"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Optic gliomas in children with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0022-3476(89)80137-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "1989"
                        "volumen" => "114"
                        "paginaInicial" => "788"
                        "paginaFinal" => "792"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Implications of new understandings of gliomas in children and adults with NF1&#58; report of a consensus conference"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/neuonc/noaa036"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuro Oncol"
                        "fecha" => "2020"
                        "volumen" => "22"
                        "paginaInicial" => "773"
                        "paginaFinal" => "784"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nonoptic pathway tumors in children with neurofibromatosis type 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000009458"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2020"
                        "volumen" => "95"
                        "paginaInicial" => "e1052"
                        "paginaFinal" => "e1059"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent&#44; refractory&#44; or progressive low-grade glioma&#58; a multicentre&#44; phase 2 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1470-2045(19)30277-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Oncol"
                        "fecha" => "2019"
                        "volumen" => "20"
                        "paginaInicial" => "1011"
                        "paginaFinal" => "1022"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Care of adults with neurofibromatosis type 1&#58; a clinical practice resource of the American College of Medical Genetics and Genomics &#40;ACMG&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/gim.2018.28"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2018"
                        "volumen" => "20"
                        "paginaInicial" => "671"
                        "paginaFinal" => "682"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased breast cancer risk in women with neurofibromatosis type 1&#58; a meta-analysis and systematic review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13053-019-0110-z"
                      "Revista" => array:5 [
                        "tituloSerie" => "Hered Cancer Clin Pract"
                        "fecha" => "2019"
                        "volumen" => "17"
                        "paginaInicial" => "12"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis and adenocarcinoma of &#40;male&#41; breast"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "AMA Arch Derm Syphilol"
                        "fecha" => "1953"
                        "volumen" => "68"
                        "paginaInicial" => "359"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type I with breast cancer&#58; not only for women&#33;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1897-4287-12-15"
                      "Revista" => array:5 [
                        "tituloSerie" => "Hered Cancer Clin Pract"
                        "fecha" => "2014"
                        "volumen" => "12"
                        "paginaInicial" => "5"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis with male breast cancer&#8212;risk factor or co-incidence&#63; Report of two rare cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3233/BD-140387"
                      "Revista" => array:6 [
                        "tituloSerie" => "Breast Dis"
                        "fecha" => "2015"
                        "volumen" => "35"
                        "paginaInicial" => "29"
                        "paginaFinal" => "32"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis type 1 and male breast cancer&#58; emerging risk factor&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/jscr/rjw138"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Surg Case Rep"
                        "fecha" => "2017"
                        "volumen" => "2017"
                        "paginaInicial" => "rjw138"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Comprehensive Cancer Network&#46; Genetic&#47;familial high-risk assessment&#58; Breast&#44; ovarian&#44; and pancreatic &#40;Version 1&#46;2022&#41;&#46; Plymouth Meeting&#58; NCCN&#59; 2021 &#91;Accessed September 2021&#93;&#46; Available on&#58; <a target="_blank" href="https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf">https&#58;&#47;&#47;www&#46;nccn&#46;org&#47;professionals&#47;physician&#95;gls&#47;pdf&#47;genetics&#95;bop&#46;pdf</a>&#46;"
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Circumstances of discovery of phaeochromocytoma&#58; a retrospective study of 41 consecutive patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1530/eje.0.1500681"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Endocrinol"
                        "fecha" => "2004"
                        "volumen" => "150"
                        "paginaInicial" => "681"
                        "paginaFinal" => "686"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pheochromocytoma and paraganglioma&#58; an endocrine society clinical practice guideline"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2014-1498"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2014"
                        "volumen" => "99"
                        "paginaInicial" => "1915"
                        "paginaFinal" => "1942"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adrenocortical carcinomas and malignant phaeochromocytomas&#58; ESMO-EURACAN Clinical Practice Guidelines for diagnosis&#44; treatment and follow up"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.annonc.2020.08.2099"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2020"
                        "volumen" => "31"
                        "paginaInicial" => "1476"
                        "paginaFinal" => "1490"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multidisciplinary practice guidelines for the diagnosis&#44; genetic counseling and treatment of pheochromocytomas and paragangliomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12094-021-02622-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Transl Oncol"
                        "fecha" => "2021"
                        "volumen" => "23"
                        "paginaInicial" => "1995"
                        "paginaFinal" => "2019"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gastrointestinal stromal tumors in patients with neurofibromatosis 1&#58; a clinicopathologic and molecular genetic study of 45 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.pas.0000176433.81079.bd"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Surg Pathol"
                        "fecha" => "2006"
                        "volumen" => "30"
                        "paginaInicial" => "90"
                        "paginaFinal" => "96"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "NF1-associated gastrointestinal stromal tumors have unique clinical&#44; phenotypic&#44; and genotypic characteristics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.pas.0000159775.77912.15"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Surg Pathol"
                        "fecha" => "2005"
                        "volumen" => "29"
                        "paginaInicial" => "1170"
                        "paginaFinal" => "1176"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gastrointestinal stromal tumours&#58; ESMO-EURACAN Clinical Practice Guidelines for diagnosis&#44; treatment and follow-up"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdy320"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2018"
                        "volumen" => "29"
                        "numero" => "Suppl 4"
                        "paginaInicial" => "iv267"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurofibromatosis and childhood leukaemia&#47;lymphoma&#58; a population-based UKCCSG study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bjc.1994.431"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Cancer"
                        "fecha" => "1994"
                        "volumen" => "70"
                        "paginaInicial" => "969"
                        "paginaFinal" => "972"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imaging evaluation of plexiform neurofibromas in neurofibromatosis type 1&#58; a survey-based assessment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000012437"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2021"
                        "volumen" => "97"
                        "numero" => "7 Suppl 1"
                        "paginaInicial" => "S111"
                        "paginaFinal" => "S119"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/22548874/0000022200000008/v1_202210061413/S225488742200042X/v1_202210061413/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "46200"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/22548874/0000022200000008/v1_202210061413/S225488742200042X/v1_202210061413/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225488742200042X?idApp=WRCEE"
]
Article information
ISSN: 22548874
Original language: English
The statistics are updated each day
Year/Month Html Pdf Total
2023 March 6 1 7
2022 September 1 2 3
2022 June 1 0 1

Follow this link to access the full text of the article

Idiomas
Revista Clínica Española (English Edition)
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?