Neurofibromatosis type 1
Autosomal dominant neurocutaneous disorder from NF1 tumor suppressor mutations causing cafe-au-lait macules, neurofibromas, Lisch nodules, and optic glioma; diagnosed clinically by consensus criteria and managed with surveillance, surgery for symptomatic tumors, and selumetinib for inoperable plexiform neurofibromas.
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What this article covers
- Overview
Definition: neurofibromatosis type 1 (NF1), also called von Recklinghausen disease, is an autosomal dominant neurocutaneous disorder caused by loss-of-function mutations in the NF1 tumor suppressor…
- Epidemiology
Birth incidence: among the most common single-gene disorders affecting the nervous system, occurring in roughly 1 in 3000 births.
- Risk factors
Family history: an affected first-degree relative confers a 50% transmission risk to each offspring given autosomal dominant inheritance.
- Pathophysiology
Gene and protein: the NF1 gene on chromosome 17q11.2 encodes neurofibromin, a GTPase-activating protein that normally accelerates conversion of active Ras-GTP to inactive Ras-GDP.
- Clinical features
Diagnostic criteria (2 or more required): six or more cafe-au-lait macules (greater than 0.5 cm in prepubertal patients, greater than 1.5 cm in postpubertal patients); two or more neurofibromas of…
- Differential diagnosis
Legius syndrome: presents with multiple cafe-au-lait macules and axillary freckling but no neurofibromas, Lisch nodules, or optic glioma; caused by a different gene (SPRED1) and confirmed by genetic testing when the phenotype is atypical.
- Diagnosis
What establishes the diagnosis: NF1 is a clinical diagnosis made when a patient meets 2 or more of the 7 consensus diagnostic criteria; genetic testing for an NF1 mutation is confirmatory but not…
- Management
First step after diagnosis: establish a multidisciplinary surveillance plan (dermatology, ophthalmology, neurology, genetics, and orthopedics as needed), since there is no cure and management is…
- Complications
Malignant peripheral nerve sheath tumor: occurs in approximately 10% of patients with NF1, typically arising within a pre-existing plexiform neurofibroma, and carries a poor prognosis once it develops.
- Prognosis
Life expectancy: modestly reduced compared with the general population, primarily driven by malignancy risk, particularly malignant peripheral nerve sheath tumor.
- Prevention
No primary prevention: because NF1 arises from germline or de novo mutation, there is no way to prevent the disease itself.
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