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
Share
Share
Download PDF
More article options
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

Purchase article

For the purchase of this article it is necessary to fill in the following form:

Afganistan
Albania
Alemania
Andorra
Angola
Anguilla
Antartica
Antigua and barbuda
Antillas holandesas
Arabia saudita
Argelia
Argentina
Armenia
Aruba
Australia
Austria
Azerbaijan
Bahamas
Bahrain
Bangladesh
Barbados
Belarus
Belgica
Belice
Benin
Bermudas/antillas britanicas
Bhutan
Bolivia
Bosnia y herzegowina
Botswana
Brasil
Brunei darussalam
Bulgaria
Burkina faso
Burundi
Cabo verde
Camboya
Camerun
Canada
Chad
Chile
China
Chipre
Colombia
Comoros
Corea
Costa rica
Cote d´ivoire
Croacia
Cuba
Dinamarca
Djibouti
Dominica
East timor
Ecuador
Egipto
El salvador
Emiratos arabes unidos
Eritrea
Escocia
Eslovaquia
Eslovenia
España
Estados federados de micronesia
Estados unidos
Estonia
Etiopia
Fiji
Filipinas
Finlandia
Francia
Gabon
Gambia
Georgia
Ghana
Gibraltar
Grecia
Grenada
Groenlandia
Guadalupe
Guam
Guatemala
Guayana britanica
Guinea
Guinea ecuatorial
Guinea francesa
Guinea-bissau
Haiti
Holanda
Honduras
Hong kong
Hungria
India
Indonesia
Irak
Iran
Irlanda
Isla bouvet
Isla cocos (keeling)
Isla cook
Isla mauricio
Isla navidad
Isla norfolk
Islandia
Islas caiman
Islas falkland (malvinas)
Islas faroe
Islas georgia del sur y sandwich
Islas heard and mc donald
Islas marshall
Islas northern mariana
Islas salomon
Islas svalbard and jan mayen
Islas turks and caicos
Islas united states minor outlyi
Islas virgenes (britanicas)
Islas virgenes (u.s.a.)
Islas wallis and futuna
Israel
Italia
Jamaica
Japon
Jordania
Kazakhstan
Kenia
Kiribati
Kuwait
Kyrgyzstan
Lesoto
Letonia
Libano
Liberia
Libia arab jamahiriya
Liechtenstein
Lituania
Luxemburgo
Macao
Macedonia
Madagascar
Malasia
Malawi
Maldives
Mali
Malta
Marruecos
Martinica
Mauritania
Mayotte
Mexico
Monaco
Mongolia
Monserrat
Morocco
Mozambique
Myanmar
Namibia
Nauru
Nepal
Nicaragua
Niger
Nigeria
Niue
Noruega
Nueva caledonia
Nueva zelanda
Oman
Pakistan
Palau
Panama
Papua new guinea
Paraguay
Peru
Pitcairn
Polinesia francesa
Polonia
Portugal
Posesiones gran bretaña
Posesiones u.s.a.
Puerto rico
Qatar
Reino unido
Republica checa
Republica de africa central
Republica de cabo verde
Republica de congo
Republica de corea
Republica de moldova
Republica democratica de laos
Republica democratica del congo
Republica dominicana
Reunion
Ruanda
Rumania
Rusia
Sahara occidental
Saint kitts and nevis
Samoa
Samoa americana
San marino
San tomas y principe
San vincent and the grenadines
Santa lucia
Senegal
Serbia
Seychelles
Sierra leona
Singapur
Siria
Somalia
Sri lanka
St. helena
St. pierre and miquelon
Sudafrica
Sudan
Suecia
Suiza
Surinam
Swaziland
Tailandia
Taiwan republica de china
Tajikistan
Tanzania
Territorio de indias britanicas
Togo
Tokelau
Tonga
Trinidad and tobago
Tunisia
Turkmenistan
Turquia
Tuvalu
Ucrania
Uganda
Uruguay
Uzbekistan
Vanuatu
Vaticano
Venezuela
Vietnam
Yemen
Yugoslavia
Zambia
Zimbawe
Lebanon
Paises bajos
A coruña
Alava
Albacete
Alicante
Almeria
Asturias
Avila
Badajoz
Balears
Barcelona
Bizkaia
Burgos
Caceres
Cadiz
Cantabria
Castellon
Ceuta
Ciudad real
Cordoba
Cuenca
Girona
Granada
Guadalajara
Guipuzcoa
Huelva
Huesca
Jaen
La rioja
Las palmas
Leon
Lleida
Lugo
Madrid
Malaga
Melilla
Murcia
Navarra
Ourense
Palencia
Pontevedra
Salamanca
Segovia
Sevilla
Soria
Tarragona
Tenerife
Teruel
Toledo
Valencia
Valladolid
Zamora
Zaragoza
-- Not applicable --
I accept to receive information about Elsevier's special products and promotions by email
I accept to receive information about products and special promotions from Elsevier partners by email
I have read and understand the Privacy Policy and Terms and conditions and agree to be bound by all of its terms.
* Required fields
In addition to temporary access to the article, it will be sent by email.
Customer Support
Phone
Calls from Spain
932 415 960
Calls from abroad
+34 932 415 960
Hours from 9 a.m. to 6 p.m. except the months of July and August, which will be from 9 am to 3 pm.
Idiomas
Revista Clínica Española (English Edition)