{"id":4422655,"date":"2025-01-12T09:15:13","date_gmt":"2025-01-12T15:15:13","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/nf1\/"},"modified":"2025-01-12T09:20:06","modified_gmt":"2025-01-12T15:20:06","slug":"nf1","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/nf1\/","title":{"rendered":"NF1"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">Overview Of NF1<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Incidence<\/strong>: ~1 in 3000 individuals<\/li>\n\n\n\n<li><strong>Inheritance<\/strong>: Autosomal dominant (approx. 50% of cases are de novo mutations)<\/li>\n\n\n\n<li><strong>Gene &amp; Protein<\/strong>: NF1 gene on chromosome 17q11.2 encodes neurofibromin, a GTPase-activating protein that downregulates Ras<\/li>\n\n\n\n<li><strong>Main Clinical Features<\/strong>\n<ul class=\"wp-block-list\">\n<li>Multiple caf\u00e9 au lait spots<\/li>\n\n\n\n<li>Axillary or inguinal freckling<\/li>\n\n\n\n<li>Neurofibromas (cutaneous, subcutaneous, plexiform)<\/li>\n\n\n\n<li>Lisch nodules (iris hamartomas)<\/li>\n\n\n\n<li>Bone abnormalities (e.g., sphenoid dysplasia, long bone bowing)<\/li>\n\n\n\n<li>Central nervous system tumors (optic gliomas, astrocytomas)<\/li>\n\n\n\n<li>Increased risk of pheochromocytoma\/paraganglioma (2% of individuals)<\/li>\n\n\n\n<li>Macrocephaly, possible cognitive deficits<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Diagnostic Criteria<\/h2>\n\n\n\n<p>At least <strong>two<\/strong> of the following must be present:<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Six or more caf\u00e9 au lait macules<\/strong> larger than 5 mm in prepubertal individuals or larger than 15 mm in postpubertal individuals<\/li>\n\n\n\n<li><strong>Two or more neurofibromas<\/strong> of any type or <strong>one plexiform neurofibroma<\/strong><\/li>\n\n\n\n<li><strong>Axillary or inguinal freckling<\/strong><\/li>\n\n\n\n<li><strong>Optic glioma<\/strong><\/li>\n\n\n\n<li><strong>Two or more Lisch nodules<\/strong> (iris hamartomas)<\/li>\n\n\n\n<li><strong>Distinctive bony lesion<\/strong>, such as sphenoid dysplasia or thinning of the cortex of long bones<\/li>\n\n\n\n<li><strong>First-degree relative<\/strong> with NF1 according to the above criteria<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Key Clinical Manifestations<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Skin Findings<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Caf\u00e9 au Lait Spots<\/strong>\n<ul class=\"wp-block-list\">\n<li>Flat, hyperpigmented lesions<\/li>\n\n\n\n<li>Appear in infancy or early childhood<\/li>\n\n\n\n<li>Six or more suggests NF1<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Freckling<\/strong>\n<ul class=\"wp-block-list\">\n<li>Dense patches in the axilla or inguinal region (pathognomonic for NF1)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Neurofibromas<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cutaneous Neurofibromas<\/strong>\n<ul class=\"wp-block-list\">\n<li>Soft, fleshy tumors on the skin surface<\/li>\n\n\n\n<li>Commonly appear in adolescence; number increases with age<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Subcutaneous Neurofibromas<\/strong>\n<ul class=\"wp-block-list\">\n<li>Firm, tender nodules along peripheral nerves<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Plexiform Neurofibromas<\/strong> (nodular or diffuse)\n<ul class=\"wp-block-list\">\n<li>May cause disfigurement and, rarely, transform into malignant peripheral nerve sheath tumors<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Lisch Nodules<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Iris Hamartomas<\/strong>\n<ul class=\"wp-block-list\">\n<li>Usually asymptomatic, identified by slit-lamp exam<\/li>\n\n\n\n<li>Raised, pigmented spots on the iris<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Skeletal Abnormalities<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sphenoid Wing Dysplasia<\/strong> \u2192 facial asymmetry<\/li>\n\n\n\n<li><strong>Long Bone Dysplasia<\/strong> \u2192 bowing, fractures<\/li>\n\n\n\n<li><strong>Vertebral Changes<\/strong> \u2192 scalloping from dural ectasia, scoliosis or kyphosis<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Nervous System Tumors<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Optic Pathway Gliomas<\/strong>\n<ul class=\"wp-block-list\">\n<li>May present with vision loss, proptosis<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Other Gliomas<\/strong> (astrocytomas, brainstem gliomas)<\/li>\n\n\n\n<li><strong>Hydrocephalus<\/strong> (rare) from aqueductal stenosis<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Other<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Pheochromocytoma\/Paraganglioma<\/strong>\n<ul class=\"wp-block-list\">\n<li>Occurs in ~2% of patients<\/li>\n\n\n\n<li>Hypertension from catecholamine excess or renal artery stenosis<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Learning Disabilities<\/strong> (mild), macrocephaly in some patients<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Genetic &amp; Molecular<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>NF1 Gene<\/strong>: Large gene on 17q11.2 with >95% mutation detection using advanced methods<\/li>\n\n\n\n<li><strong>Neurofibromin<\/strong>: A Ras GTPase-activating protein; loss causes increased Ras signaling<\/li>\n\n\n\n<li><strong>Inheritance<\/strong>: 50% familial; 50% de novo<\/li>\n\n\n\n<li><strong>Genotype-Phenotype<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Rarely a single known correlation: a 3-bp deletion (c.2970-2972 delAAT) is associated with few or no cutaneous neurofibromas<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Management &amp; Surveillance<\/h2>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Clinical Evaluations<\/strong>\n<ul class=\"wp-block-list\">\n<li>Annual blood pressure checks (pheochromocytoma risk)<\/li>\n\n\n\n<li>Neurologic and skin exams<\/li>\n\n\n\n<li>Eye exams to screen for optic gliomas<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Imaging<\/strong>\n<ul class=\"wp-block-list\">\n<li>MRI of the brain or orbit if symptoms suggest optic pathway glioma or other CNS tumors<\/li>\n\n\n\n<li>Imaging of suspicious neurofibromas or skeletal lesions<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Genetic Testing &amp; Counseling<\/strong>\n<ul class=\"wp-block-list\">\n<li>Helpful in uncertain cases or family planning<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Surgical Interventions<\/strong>\n<ul class=\"wp-block-list\">\n<li>Resection of symptomatic or suspicious plexiform neurofibromas<\/li>\n\n\n\n<li>Address skeletal deformities if severe<\/li>\n\n\n\n<li>Resection or medical management of pheochromocytoma<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<p>Patients with NF1 require a multidisciplinary approach (neurologists, geneticists, ophthalmologists, orthopedic surgeons, oncologists) for lifelong monitoring to manage and promptly treat complications.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Overview Of NF1 Diagnostic Criteria At least two of the following must be present: Key Clinical Manifestations Skin Findings Neurofibromas Lisch Nodules Skeletal Abnormalities Nervous System Tumors Other Genetic &amp; Molecular Management &amp; Surveillance Patients with NF1 require a multidisciplinary approach (neurologists, geneticists, ophthalmologists, orthopedic surgeons, oncologists) for lifelong monitoring to manage and promptly treat [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[690],"class_list":["post-4422655","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-rare-genetic-conditions","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422655","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":2,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422655\/revisions"}],"predecessor-version":[{"id":4422658,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422655\/revisions\/4422658"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422655"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422655"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}