{"id":74,"date":"2021-11-27T15:50:10","date_gmt":"2021-11-27T14:50:10","guid":{"rendered":"https:\/\/cerenef.org\/?page_id=74"},"modified":"2025-10-04T14:20:56","modified_gmt":"2025-10-04T12:20:56","slug":"neurofibromatose-de-type-1","status":"publish","type":"post","link":"https:\/\/cerenef.org\/en\/neurofibromatose-de-type-1\/","title":{"rendered":"Neurofibromatosis type 1"},"content":{"rendered":"<div data-elementor-type=\"wp-page\" data-elementor-id=\"74\" class=\"elementor elementor-74\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-d4e98c4 elementor-section-boxed elementor-section-height-default elementor-section-height-default elementor-invisible\" data-id=\"d4e98c4\" data-element_type=\"section\" data-e-type=\"section\" data-settings=\"{&quot;animation&quot;:&quot;fadeInLeft&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-7f24ea0\" data-id=\"7f24ea0\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-887fea6 elementor-widget elementor-widget-image\" data-id=\"887fea6\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"Neurofibromatosis type 1\" title=\"Neurofibromatosis type 1\" alt=\"Neurofibromatose de type 1\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-5a3607b elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"5a3607b\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-d80ffb8\" data-id=\"d80ffb8\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-414bdfc elementor-widget elementor-widget-heading\" data-id=\"414bdfc\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Epidemiology and diagnostic criteria<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-707e44c elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"707e44c\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-49ff3ca\" data-id=\"49ff3ca\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap\">\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-d5ab112 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"d5ab112\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-9c1a5b7\" data-id=\"9c1a5b7\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-75c9df9 elementor-widget elementor-widget-heading\" data-id=\"75c9df9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Complications<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-b5eb2c9 elementor-widget elementor-widget-toggle\" data-id=\"b5eb2c9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"toggle.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1901\" class=\"elementor-tab-title\" data-tab=\"1\" role=\"button\" aria-controls=\"elementor-tab-content-1901\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Epidemiology<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1901\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"1\" role=\"region\" aria-labelledby=\"elementor-tab-title-1901\"><p>Neurofibromatosis type 1 (NF1) is a genetic disease of autosomal dominant inheritance, linked to a mutation in the NF1 gene <em>NF1<\/em> encoding neurofibromin. The genetics of neurofibromatosis is included in a dedicated chapter. Its prevalence is 1\/4000 <sup>1\u20134<\/sup> and its incidence estimated at one in 3000 births. \u00a0<sup>1,2,5\u20137<\/sup>Its phenotypic expression is variable even between members of a family. Its penetrance is complete at the age of 8 years: 97% of patients with NF1 meet the diagnostic criteria at 8 years <sup>8<\/sup>.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1902\" class=\"elementor-tab-title\" data-tab=\"2\" role=\"button\" aria-controls=\"elementor-tab-content-1902\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Diagnostic criteria<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1902\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"2\" role=\"region\" aria-labelledby=\"elementor-tab-title-1902\"><p>The diagnosis is based on the combination of at least 2 of the 7 NIH criteria from 1988<sup>9<\/sup> revised in 2021<sup>10<\/sup>, and summarized below. They differ depending on whether the patient has one of his two parents also affected.<\/p><p><strong>REVISED DIAGNOSTIC CRITERIA FOR NF1<br \/><\/strong><strong>(1988 NIH CONSENSUS CONFERENCE, REVISED IN 2021)<\/strong><\/p><p><strong>A. The diagnostic criteria for NF1 are met in an individual who does not have a parent diagnosed with NF1 if two or more of the following are present:<\/strong><\/p><ul><li>Six or more \"caf\u00e9-au-lait\" macules over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals.<\/li><li>Freckling in the axillary or inguinal region.* #<\/li><li>Two or more neurofibromas of any type or one plexiform neurofibroma.<\/li><li>Optic pathway glioma.<\/li><li>Two or more iris Lisch nodules identified by slit lamp examination or two or more choroidal abnormalities (CAs)\u2014defined as bright, patchy nodules imaged by optical coherence tomography (OCT)\/near-infrared reflectance (NIR) imaging.<\/li><li>A distinctive osseous lesion such as sphenoid dysplasia***, anterolateral bowing of the tibia, or pseudarthrosis of a long bone.<\/li><li>A heterozygous pathogenic <em>NF1<\/em>NF1 variant with a variant allele fraction of 50% in apparently normal tissue such as white blood cells.<\/li><\/ul><p><strong>B. A child of a parent who meets the diagnostic criteria specified in A merits a diagnosis of NF1 if one or more of the criteria in A are present. <\/strong><\/p><p><em>* : If only caf\u00e9-au-lait macules and freckling are present, the diagnosis is most likely NF1 but exceptionally the person might have another diagnosis such as Legius syndrome.<\/em><br \/><em># : At least one of the two pigmentary findings (caf\u00e9-au-lait macules or freckling) should be bilateral.<\/em><br \/><em>** : Sphenoid wing dysplasia is not a separate criterion in case of an ipsilateral orbital plexiform neurofibroma.<\/em><\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1903\" class=\"elementor-tab-title\" data-tab=\"3\" role=\"button\" aria-controls=\"elementor-tab-content-1903\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Illustrative photographs - Dermatology Department Collection (Henri-Mondor Hospital)<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1903\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"3\" role=\"region\" aria-labelledby=\"elementor-tab-title-1903\"><p><div id='gallery-1' class='gallery galleryid-74 gallery-columns-5 gallery-size-full'><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/neurofibrome-cutanes-.jpg\" class=\"attachment-full size-full\" alt=\"Neurofibromes cutan\u00e9s chez un adulte\" aria-describedby=\"gallery-1-2192\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2192'>\n\t\t\t\tCutaneous neurofibromas (adult)\n\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/neurofibrome-cutanes-1.jpg\" class=\"attachment-full size-full\" alt=\"Neurofibromes cutan\u00e9s chez un adulte\" aria-describedby=\"gallery-1-2193\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2193'>\n\t\t\t\tCutaneous neurofibromas (adult)\n\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/neurofibrome-plexiforme-cervical.jpg\" class=\"attachment-full size-full\" alt=\"Neurofibrome plexiforme cervical post\u00e9rieur (adulte)\" aria-describedby=\"gallery-1-2200\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2200'>\n\t\t\t\tPosterior cervical plexiform neurofibroma (adult)\n\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/Lentigines-axillaires-1.jpg\" class=\"attachment-full size-full\" alt=\"Lentigines axillaires (adulte)\" aria-describedby=\"gallery-1-2201\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2201'>\n\t\t\t\tFreckling in the axillary region (adult)\n\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/Lentigines-axillaires-2.jpg\" class=\"attachment-full size-full\" alt=\"Lentigines axillaires (adulte)\" aria-describedby=\"gallery-1-2202\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2202'>\n\t\t\t\tFreckling in the axillary region (adult)\n\t\t\t\t<\/dd><\/dl><br style=\"clear: both\" \/><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/cafe-lait-1.jpg\" class=\"attachment-full size-full\" alt=\"Tache caf\u00e9 au lait associ\u00e9e \u00e0 des neurofibromes cutan\u00e9s (adulte)\" aria-describedby=\"gallery-1-2203\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2203'>\n\t\t\t\t\"Caf\u00e9-au-lait\" macules associated with cutaneous neurofibromas\n\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/cafe-lait-2.jpg\" class=\"attachment-full size-full\" alt=\"Large tache caf\u00e9 au lait (adulte)\" aria-describedby=\"gallery-1-2204\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2204'>\n\t\t\t\tLarge \"caf\u00e9-au-lait\" macules (adult)\n\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/cafe-lait-3.jpg\" class=\"attachment-full size-full\" alt=\"Taches caf\u00e9 au lait associ\u00e9es \u00e0 des lentigines axillaires bilat\u00e9rales (enfant)\" aria-describedby=\"gallery-1-2205\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2205'>\n\t\t\t\t\"Caf\u00e9-au-lait\" macules associated with\nfreckling in the bilateral axillary region(child)\n\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/cafe-lait-4.jpg\" class=\"attachment-full size-full\" alt=\"Taches caf\u00e9 a -lait associ\u00e9es \u00e0 des lentigines axillaires bilat\u00e9rales (enfant)\" aria-describedby=\"gallery-1-2206\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2206'>\n\t\t\t\t\"Caf\u00e9-au-lait\" macules associated with\nfreckling in the bilateral axillary region(child)\n\t\t\t\t<\/dd><\/dl><dl class='gallery-item'>\n\t\t\t<dt class='gallery-icon portrait'>\n\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"140\" height=\"200\" src=\"https:\/\/cerenef.org\/wp-content\/uploads\/2022\/01\/lish.jpg\" class=\"attachment-full size-full\" alt=\"Nodules de Lisch (examen \u00e0 la lampe \u00e0 fente)\" aria-describedby=\"gallery-1-2207\" \/>\n\t\t\t<\/dt>\n\t\t\t\t<dd class='wp-caption-text gallery-caption' id='gallery-1-2207'>\n\t\t\t\tLisch nodules (slit lamp examination)\n\t\t\t\t<\/dd><\/dl><br style=\"clear: both\" \/>\n\t\t<\/div>\n<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-48a1223 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"48a1223\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-6d4c9b7\" data-id=\"6d4c9b7\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-b80edd9 elementor-widget elementor-widget-text-editor\" data-id=\"b80edd9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>The disease complications are numerous, benign or malignant, somatic and psychological, and appear throughout the lifespan<sup>11<\/sup>. However, one of the peculiarities of NF1 remains its variability of expression from one patient to another and even within a family (where the genetic abnormality is identical). This makes it impossible to predict the clinical course of an affected child.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-565e2b2 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"565e2b2\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-7f57a52\" data-id=\"7f57a52\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-90d5e8f elementor-widget elementor-widget-toggle\" data-id=\"90d5e8f\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"toggle.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1511\" class=\"elementor-tab-title\" data-tab=\"1\" role=\"button\" aria-controls=\"elementor-tab-content-1511\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Neurofibromas <\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1511\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"1\" role=\"region\" aria-labelledby=\"elementor-tab-title-1511\"><p>There are different types of neurofibromas: dermal (&gt;95% of patients)<sup>12,13<\/sup>, peripheral nodular (at least 20% of patients)<sup>12<\/sup>and nodular orplexiform (20% of patients)<sup>14<\/sup>The main risk, inherent in nodular and plexiform neurofibromas, is the transformation into a malignant peripheral nerve sheath tumour (MPNST, formerly known as malignant nerve sheath tumour). The cumulative risk of developing MPNST during a patient's lifetime has been estimated to be 8-16%. It occurs mostly between 20 and 35 years of age. <sup>15\u201319<\/sup>This risk is increased in patients with an NF1 phenotype, defined by the presence of subcutaneous neurofibromas: in case of subcutaneous neurofibromas, the risk of developing an internal plexiform neurofibroma or MPNST is multiplied by 3, and in case of plexiform neurofibroma, the risk of developing an MPNST is multiplied by 20<sup>20<\/sup>The tumour may be aggressive17, with a decreased life expectancy. Metabolic imaging such as PET-MRI or PET-scanner can diagnose a neurofibroma in the dysplastic stage and thus improve the prognosis through early surgery. Neurofibromas can also have a significant aesthetic and functional impact.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1512\" class=\"elementor-tab-title\" data-tab=\"2\" role=\"button\" aria-controls=\"elementor-tab-content-1512\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Optic pathway glioma<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1512\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"2\" role=\"region\" aria-labelledby=\"elementor-tab-title-1512\"><p>Optic pathway glioma <sup>22\u201326<\/sup> is a benign tumour with low malignancy potential present in 15-20% of children with NF1 <sup>22,27\u201331<\/sup>. On the other hand, its local extension can lead to exophthalmos, decreased visual acuity, or compression of the optic chiasma with possible repercussions on the gonadotropic hypothalamic-pituitary axis and early puberty <sup>31,32<\/sup>.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1513\" class=\"elementor-tab-title\" data-tab=\"3\" role=\"button\" aria-controls=\"elementor-tab-content-1513\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Dysplasia of long bones, pseudarthrosis, and dystrophic scoliosis<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1513\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"3\" role=\"region\" aria-labelledby=\"elementor-tab-title-1513\"><p>Orthopaedic disorders are classic: congenital dysplasia of long bones (7.2% of patients) <sup>33<\/sup>, sphenoidal dysplasia (1 to 7% of patients) <sup>34<\/sup> and scoliosis (10 to 28% of patients) <sup>35<\/sup>. Congenital long bone dysplasia causes deformity, and an increased risk of fracture with pseudoarthrosis in 2 to 3.6% of patients <sup>33,36<\/sup>Sphenoidal dysplasia can be secondary to plexiform neurofibroma <sup>37<\/sup>, and can lead to pulsatile exophthalmos without decreased visual acuity and a hernia of the temporal lobe in the eyeball in case of total absence of sphenoid bone <sup>38<\/sup>. Scoliosis, the most common orthopaedic manifestation, is often associated with vertebral dysplasia <sup>39<\/sup>Patients with NF1 appear to be at increased risk of weakening osteopathy, with osteopenia presentin 48% of patients or osteoporosis in 25% <sup>40,41<\/sup>.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1514\" class=\"elementor-tab-title\" data-tab=\"4\" role=\"button\" aria-controls=\"elementor-tab-content-1514\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Early puberty<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1514\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"4\" role=\"region\" aria-labelledby=\"elementor-tab-title-1514\"><p>Early stunting is present in one-third of children <sup>42<\/sup>, precocious puberty can also occur <sup>34,43<\/sup>. Precocious puberty is defined by the appearance of sexual criteria before the age of 7-8 years in girls and 9-10 years in boys.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1515\" class=\"elementor-tab-title\" data-tab=\"5\" role=\"button\" aria-controls=\"elementor-tab-content-1515\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">High blood pressure and vascular dysplasia<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1515\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"5\" role=\"region\" aria-labelledby=\"elementor-tab-title-1515\"><p>Cardiovascular complications are mainly linked to essential or secondary hypertension, which can begin in childhood (16 to 19% of children with NF1) and whose risk increases with age <sup>44\u201348<\/sup>. Secondary causes of high blood pressure associated with NF1 include:  vascular nephropathy, paraganglioma, pheochromocytoma, or coarctation of the aorta. Congenital heart defects have also been reported in 0.4 to 8.6% of patients. <sup>49\u201354<\/sup>There is also a significant risk of bleeding, particularly during neurofibroma surgery <sup>55<\/sup>\u00a0; risk attributed to vascular dysplasia and primary hemostasis abnormalities <sup>56<\/sup>.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1516\" class=\"elementor-tab-title\" data-tab=\"6\" role=\"button\" aria-controls=\"elementor-tab-content-1516\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Epilepsy<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1516\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"6\" role=\"region\" aria-labelledby=\"elementor-tab-title-1516\"><p>Epilepsy and its developmental repercussions are the most severe central neurological complication. Epilepsy affects 8% of patients <sup>57,58<\/sup>, and is resistant to treatment in 30% of cases <sup>59<\/sup>. In the latter cases, it can be associated with severe mental retardation.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1517\" class=\"elementor-tab-title\" data-tab=\"7\" role=\"button\" aria-controls=\"elementor-tab-content-1517\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Learning difficulties<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1517\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"7\" role=\"region\" aria-labelledby=\"elementor-tab-title-1517\"><p>Moderate cognitive impairment, outside of epilepsy, is the most common neurological complication <sup>60<\/sup>, with an intelligence quotient in the lower middle part, behavioural disorders, and specific learning difficulties (visuospatial and visuomotor disorders, language disorders, fine and gross motor disorders, and executive function disorders)<sup>5,60\u201365<\/sup>. Other pathologies have also been associated with NF1, including attention deficit\/hyperactivity, autistic, and psychosocial disorders <sup>63,65<\/sup>.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1518\" class=\"elementor-tab-title\" data-tab=\"8\" role=\"button\" aria-controls=\"elementor-tab-content-1518\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Cancer risk<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1518\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"8\" role=\"region\" aria-labelledby=\"elementor-tab-title-1518\"><p>Finally, patients with NF1 have an increased risk of neoplasia <sup>66<\/sup>. Concerning the risk of breast cancer, particularly studied in the NF1 patient population, it occurs in women under 50 years of age <sup>67\u201371<\/sup> with a higher mortality rate\u00a0<sup>72<\/sup>. These characteristics justify the need of systematic annual screening by combining mammography-ultrasounds <sup>73<\/sup> et d\u2019une IRM mammaire, \u00e0 partir de l\u2019\u00e2ge de 30 ans chez les femmes atteintes de NF1. Les TMGN repr\u00e9sentent 60% des cancers dans cette population mais les patients peuvent \u00e9galement d\u00e9velopper d\u2019autres tumeurs du spectre neurologique\u00a0: les tumeurs c\u00e9r\u00e9brales, dont les gliomes des voies optiques, mais aussi les gliomes du tronc c\u00e9r\u00e9bral <sup>74<\/sup>, or gastrointestinal neuroendocrine tumours, which often occur at a younger age than that of the general population and that are often multiple and regularly located in the small intestine <sup>75,76<\/sup><\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1519\" class=\"elementor-tab-title\" data-tab=\"9\" role=\"button\" aria-controls=\"elementor-tab-content-1519\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Psychosocial consequences<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1519\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"9\" role=\"region\" aria-labelledby=\"elementor-tab-title-1519\"><p>The chronic psychological repercussions of NF1 have been the subject of two studies evaluating anxio-depressive disorders in adults <sup>77<\/sup>, and children <sup>78<\/sup>\u00a0: 19% of adults reported depressive symptoms and 15% anxiety disorders <sup>77<\/sup>. In adults, the associations between the severity of anxio-depressive symptoms and the severity of the disease (calculated by a modified version of the Riccardi score <sup>79<\/sup>) or the visibility of skin lesions (calculated according to the Ablon score <sup>80<\/sup>) are significant (p&lt;0.001) <sup>77<\/sup>.<\/p><p>Sleep disturbances in patients with NF1 have also been evaluated in one study in adults <sup>81<\/sup> and another one in children <sup>65<\/sup>The mean scores of ESS (<em>Epworth Sleepiness Scale<\/em>) <sup>82<\/sup> and PSQI (<em>Pittsburgh Sleep Quality Index)<\/em>) <sup>83<\/sup> which assess sleep disturbances, are abnormally high in these patients <sup>81<\/sup>, with no correlation between the two scores.<\/p><p>In children with NF1, conduct problems (p \u00a3 0.05), hyperactivity (p \u00a3 0.01), emotional fragility (p \u00a3 0.01) and total difficulty score (p \u00a3 0.01) are significantly increased and correlated with sleep disturbances <sup>65<\/sup>. These psychological and sleep impacts, associated with chronic pain, significantly contribute to the impairment of the quality of life of patients with NF1 <sup>84\u201386<\/sup>Adaptation of the quality of life (Skindex-16) and burden scores are underway for NF1: CutNF-Skindex and Burden of NF1 respectively.<\/p><p>The long-term management of these patients must integrate this dimension.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-15110\" class=\"elementor-tab-title\" data-tab=\"10\" role=\"button\" aria-controls=\"elementor-tab-content-15110\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Morbidity and mortality during neurofibromatosis type 1 <\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-15110\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"10\" role=\"region\" aria-labelledby=\"elementor-tab-title-15110\"><p>The risk of mortality is increased in patients with NF1. Compared to the general population, their life expectancy is shortened by 10 to 15 years <sup>15,67,68,72,87\u201389<\/sup>. In France, the last NF1 mortality study dates from 2011 <sup>89<\/sup>and concerned data from 1985 patients between 1980 and 2005. All-cause mortality was significantly higher in the NF1 patient cohort, with a SMR (<em>Standardized Mortality Ratio)<\/em>of 2.02 (1.6-2.6) (p &lt;0.0001). The main cause of death, available for 58 patients (86.6% of patients who died), was MPNST.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-4f7c50c elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"4f7c50c\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-1904d36\" data-id=\"1904d36\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-7148680 elementor-widget elementor-widget-heading\" data-id=\"7148680\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Main differential diagnosis <\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-873a1d9 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"873a1d9\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-150d3a6\" data-id=\"150d3a6\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-78398b4 elementor-widget elementor-widget-toggle\" data-id=\"78398b4\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"toggle.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-1261\" class=\"elementor-tab-title\" data-tab=\"1\" role=\"button\" aria-controls=\"elementor-tab-content-1261\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Legius Syndrome<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-1261\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"1\" role=\"region\" aria-labelledby=\"elementor-tab-title-1261\"><p>The main differential diagnosis of neurofibromatosis type 1 (NF1) is Legius syndrome. Like the diagnostic criteria for NF1, those for Legius syndrome are divided into two scenarios (A and B) depending on the absence (A) or presence (B) of an affected parent.\u00a0<\/p><p>Thus, the diagnosis of Legius syndrome is made under the following conditions:<\/p><ol><li>The diagnostic criteria for Legius syndrome are met in an individual who does not have a parent diagnosed with Legius syndrome if the following criteria are present:<\/li><\/ol><ul><li>Six or more \"caf\u00e9-au-lait\" macules bilaterally distributed and no other NF1-related diagnostic criteria except for axillaryor inguinal freckling.<\/li><li>A heterozygous pathogenic <em>SPRED1<\/em>NF1 variant with a variant allele fraction of 50% in apparently normal tissue such as white blood cells.<\/li><\/ul><ol><li>A child of a parent who meets the diagnostic criteria specified in A merits a diagnosis of NF1 if one or more of the criteria in A are present.<\/li><\/ol><p>The presence of fewer than six caf\u00e9-au-lait macules does not exclude Legius syndrome.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-e696eb4 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"e696eb4\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-6fc6f74\" data-id=\"6fc6f74\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-22174c1 elementor-widget elementor-widget-heading\" data-id=\"22174c1\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Patient care<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-a1c0382 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"a1c0382\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-f03b8a7\" data-id=\"f03b8a7\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-f8791d2 elementor-widget elementor-widget-toggle\" data-id=\"f8791d2\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"toggle.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-2601\" class=\"elementor-tab-title\" data-tab=\"1\" role=\"button\" aria-controls=\"elementor-tab-content-2601\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">The patient journey<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-2601\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"1\" role=\"region\" aria-labelledby=\"elementor-tab-title-2601\"><p>For the most symptomatic forms, NF1 requires multidisciplinary and multi-professional monitoring over the longterm, with specific research of the various above-mentioned complications and appropriate support, sometimes from an early age (with learning support, for instance).<\/p><p>This care is routinely organized near patients with reference to the appropriate referral centre of neurofibromatosis, when necessary.<\/p><p>The National Diagnostic and Care Protocols (\"Protocoles Nationaux de Diagnostic et de Soin\", PNDS) was updated in 2021, and it is available on <a href=\"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-020-1310-3\" target=\"_blank\" rel=\"noopener\">the French High Authority of Health website<\/a> or on <a href=\"#\">the page<\/a> of useful documents for healthcare professionals.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-2602\" class=\"elementor-tab-title\" data-tab=\"2\" role=\"button\" aria-controls=\"elementor-tab-content-2602\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Treatment<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-2602\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"2\" role=\"region\" aria-labelledby=\"elementor-tab-title-2602\"><p>These complications are most often not specific to NF1, and their management does not differ from the same situations encountered in patients without NF1. However, several cases need to be clarified.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-2603\" class=\"elementor-tab-title\" data-tab=\"3\" role=\"button\" aria-controls=\"elementor-tab-content-2603\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Pain<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-2603\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"3\" role=\"region\" aria-labelledby=\"elementor-tab-title-2603\"><p>Pain is a very common symptom of NF1 and can accompany, or even reveal, many complications. The neuropathic component of pain is preponderant when it is secondary to compressive and\/or transformed internal neurofibromas. The use of active treatments on neuropathic pain, in addition to conventional analgesics, is therefore essential for patients with NF1. These treatments include drugs from the family of antiepileptics and\/or antidepressants.<\/p><p>For adult patients, many hospitals offer specialised pain management. Referral and competence centres most often work with a pain management team from the same hospital. For patients suffering from chronic pain in the Paris region, they can contact a specialised structure within the AP-HP, on this <a href=\"https:\/\/www.aphp.fr\/douleur\" target=\"_blank\" rel=\"noopener\">link.<\/a>.<\/p><p>The assessment and management of children's pain is complex and most often involves multidisciplinary and multi-professional teams. Various websites can help parents, but healthcare professionals may also contribute to the assessment and management of pain, such as:<\/p><ul><li style=\"list-style-type: none;\"><ul><li><a href=\"https:\/\/pediadol.org\" target=\"_blank\" rel=\"noopener\">pediadol.org<\/a><\/li><li><a href=\"https:\/\/douleur-chronique-enfant.org\" target=\"_blank\" rel=\"noopener\">douleur-chronique-enfant.org<\/a><\/li><\/ul><\/li><\/ul><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-2604\" class=\"elementor-tab-title\" data-tab=\"4\" role=\"button\" aria-controls=\"elementor-tab-content-2604\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Malignant peripheral nerve sheath tumours (MPNSTs)<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-2604\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"4\" role=\"region\" aria-labelledby=\"elementor-tab-title-2604\"><p>Malignant peripheral nerve sheaths tumours (MPNSTs) are serious complications whose prognosis depends on the possibility of performing a broad surgical excision. After surgical treatment, when possible, adjuvant radiotherapy is most often offered. In case of a locally advanced and inoperable disease, or in the metastatic stage, poly-chemotherapy is proposed.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-2605\" class=\"elementor-tab-title\" data-tab=\"5\" role=\"button\" aria-controls=\"elementor-tab-content-2605\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Cutaneous neurofibromas<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-2605\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"5\" role=\"region\" aria-labelledby=\"elementor-tab-title-2605\"><p>Cutaneous neurofibromas rarely evolve into MPNST, but they can be responsible for major aesthetic discomfort. The only treatments currently available are interventional treatments: CO2 laser<sub>2<\/sub>, conventional surgical excision, and electro-dissection. Aesthetic results depend on the quality of healing and the number of lesions to be treated.<\/p><p>\u00a0<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-2606\" class=\"elementor-tab-title\" data-tab=\"6\" role=\"button\" aria-controls=\"elementor-tab-content-2606\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Plexiform neurofibromas <\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-2606\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"6\" role=\"region\" aria-labelledby=\"elementor-tab-title-2606\"><p>Although the surgical treatment remains the first choice in the management of symptomatic plexiform neurofibromas, their partial or complete resection is not always feasible.\nIn this context, several molecules have emerged, in particular MEK inhibitors. Multiple studies have demonstrated their efficacy as a treatment for symptomatic and inoperable internal neurofibromas.<sup>90\u201393<\/sup>. In 2021, selumetinib received marketing authorization at the European level for the following indication: inoperable plexiform neurofibromas in children. In 2023, its reimbursement was approved by social security. In 2025, selumetinib was recommended for approval in the European Union for the treatment of symptomatic and inoperable plexiform neurofibromas in adults with NF1. This recommendation by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency is based on the results of the KOMET Phase III trial, a global Phase III, placebo-controlled, double-blind study conducted in adults with this condition. The trial demonstrated a statistically significant objective response rate of 20% in tumor size reduction.<sup>94<\/sup>In France, it is now possible to prescribe selumetinib as part of an early access program, prior to full marketing authorization, in adults. These treatments may be prescribed in specialized centers after multidisciplinary team discussions (RCP).<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-615986e elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"615986e\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-97db34e\" data-id=\"97db34e\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-b09b44f elementor-widget elementor-widget-heading\" data-id=\"b09b44f\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Bibliographic references<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-1b1774d elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"1b1774d\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-a5f4766\" data-id=\"a5f4766\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-3972db7 elementor-widget elementor-widget-toggle\" data-id=\"3972db7\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"toggle.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle\">\n\t\t\t\t\t\t\t<div class=\"elementor-toggle-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-6021\" class=\"elementor-tab-title\" data-tab=\"1\" role=\"button\" aria-controls=\"elementor-tab-content-6021\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon elementor-toggle-icon-left\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-closed\"><i class=\"fas fa-caret-right\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-toggle-icon-opened\"><i class=\"elementor-toggle-icon-opened fas fa-caret-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-toggle-title\" tabindex=\"0\">Bibliographic references<\/a>\n\t\t\t\t\t<\/div>\n\n\t\t\t\t\t<div id=\"elementor-tab-content-6021\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"1\" role=\"region\" aria-labelledby=\"elementor-tab-title-6021\"><ol><li>Lammert M, Friedman JM, Kluwe L, Mautner VF. 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Detecting anxiety symptoms in children and youths with neurofibromatosis type I. <em>Am J Med Genet Part B Neuropsychiatr Genet Off Publ Int Soc Psychiatr Genet<\/em>. 2012;159B(7):869-873. doi:10.1002\/ajmg.b.32095<\/li><li>Barton B, North K. The self-concept of children and adolescents with neurofibromatosis type 1. <em>Child Care Health Dev<\/em>. 2007;33(4):401-408. doi:10.1111\/j.1365-2214.2006.00717.x<\/li><li>Ablon J. Gender response to neurofibromatosis 1. <em>Soc Sci Med 1982<\/em>. 1996;42(1):99-109. doi:10.1016\/0277-9536(95)00076-3<\/li><li>Leschziner GD, Golding JF, Ferner RE. Sleep disturbance as part of the neurofibromatosis type 1 phenotype in adults. <em>Am J Med Genet A<\/em>. 2013;161A(6):1319-1322. doi:10.1002\/ajmg.a.35915<\/li><li>Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. <em>Sleep<\/em>. 1991;14(6):540-545. doi:10.1093\/sleep\/14.6.540<\/li><li>Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. <em>Psychiatry Res<\/em>. 1989;28(2):193-213. doi:10.1016\/0165-1781(89)90047-4<\/li><li>Vranceanu AM, Merker VL, Park E, Plotkin SR. Quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis: a systematic review of the literature. <em>J Neurooncol<\/em>. 2013;114(3):257-262. doi:10.1007\/s11060-013-1195-2<\/li><li>Vranceanu AM, Merker VL, Park ER, Plotkin SR. Quality of life among children and adolescents with neurofibromatosis 1: a systematic review of the literature. <em>J Neurooncol<\/em>. 2015;122(2):219-228. doi:10.1007\/s11060-015-1725-1<\/li><li>Garwood MM, Bernacki JM, Fine KM, Hainsworth KR, Davies WH, Klein-Tasman BP. Physical, cognitive, and psychosocial predictors of functional disability and health-related quality of life in adolescents with neurofibromatosis-1. <em>Pain Res Treat<\/em>. 2012;2012:975364. doi:10.1155\/2012\/975364<\/li><li>Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: an analysis using U.S. death certificates. <em>Am J Hum Genet<\/em>. 2001;68(5):1110-1118. doi:10.1086\/320121<\/li><li>Z\u00f6ller M, Rembeck B, Akesson HO, Angervall L. Life expectancy, mortality and prognostic factors in neurofibromatosis type 1. A twelve-year follow-up of an epidemiological study in G\u00f6teborg, Sweden. <em>Acta Derm Venereol<\/em>. 1995;75(2):136-140. doi:10.2340\/0001555575136140<\/li><li>Duong TA, Sbidian E, Valeyrie-Allanore L, et al. Mortality associated with neurofibromatosis 1: a cohort study of 1895 patients in 1980-2006 in France. <em>Orphanet J Rare Dis<\/em>. 2011;6:18. doi:10.1186\/1750-1172-6-18<\/li><li>Dombi E, Baldwin A, Marcus LJ, et al. Activity of Selumetinib in Neurofibromatosis Type 1\u2013Related Plexiform Neurofibromas. https:\/\/doi.org\/10.1056\/NEJMoa1605943. doi:10.1056\/NEJMoa1605943<\/li><li>Weiss BD, Wolters PL, Plotkin SR, et al. NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas. <em>J Clin Oncol Off J Am Soc Clin Oncol<\/em>. 2021;39(7):797-806. doi:10.1200\/JCO.20.02220<\/li><li>Gross AM, Wolters PL, Dombi E, et al. Selumetinib in Children with Inoperable Plexiform Neurofibromas. <em>N Engl J Med<\/em>. 2020;382(15):1430-1442. doi:10.1056\/NEJMoa1912735<\/li><li>Fisher MJ, Shih CS, Rhodes SD, et al. Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial. <em>Nat Med<\/em>. 2021;27(1):165-173. doi:10.1038\/s41591-020-01193-6<\/li><li>Chen AP, Coyne GO, Wolters PL, et al. Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas (KOMET): a multicentre, international, randomised, placebo-controlled, parallel, double-blind, phase 3 study. <em>Lancet Lond Engl<\/em>. 2025;405(10496):2217-2230. doi:10.1016\/S0140-6736(25)00986-9<\/li><\/ol><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>","protected":false},"excerpt":{"rendered":"<p>\u00c9pid\u00e9miologie et crit\u00e8res diagnostiques Complications \u00c9pid\u00e9miologie La neurofibromatose de type 1 (NF1) est une maladie g\u00e9n\u00e9tique de transmission autosomique dominante, li\u00e9e \u00e0 une mutation du g\u00e8ne NF1 codant la neurofibromine. La g\u00e9n\u00e9tique des neurofibromatoses est reprise dans un chapitre d\u00e9di\u00e9. Sa pr\u00e9valence est de 1\/4000 1\u20134 et son incidence estim\u00e9e \u00e0 une naissance sur 3000&hellip;&nbsp;<\/p>\n<div class=\"read-more-wrapper\"><a href=\"https:\/\/cerenef.org\/en\/neurofibromatose-de-type-1\/\" class=\"button button-secondary\" rel=\"bookmark\">\u279c Read more<span class=\"screen-reader-text\">Neurofibromatosis type 1<\/span><\/a><\/div>","protected":false},"author":1,"featured_media":3531,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"neve_meta_sidebar":"","neve_meta_container":"","neve_meta_enable_content_width":"off","neve_meta_content_width":100,"neve_meta_title_alignment":"","neve_meta_author_avatar":"","neve_post_elements_order":"","neve_meta_disable_header":"","neve_meta_disable_footer":"","neve_meta_disable_title":"","neve_meta_reading_time":"","footnotes":""},"categories":[17],"tags":[],"class_list":["post-74","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-les-neurofibromatoses"],"_links":{"self":[{"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/posts\/74","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/comments?post=74"}],"version-history":[{"count":12,"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/posts\/74\/revisions"}],"predecessor-version":[{"id":4168,"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/posts\/74\/revisions\/4168"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/media\/3531"}],"wp:attachment":[{"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/media?parent=74"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/categories?post=74"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cerenef.org\/en\/wp-json\/wp\/v2\/tags?post=74"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}