Type 1 neurofibromatosis (NF1) is an autosomal-dominant genetic disorder with the defining features of café au lait spots, multiple neurofibromas, and iris Lisch nodules.
Diagnosis is made clinically; RNA-based NF1 mutation molecular testing to confirm the diagnosis is recommended.
The disorder is progressive, though variable; it will worsen.
Multiple organ systems are involved: skin, central nervous system, peripheral nerves, eyes, bones, gastrointestinal tract, and vascular and endocrine systems.
Presentation in a young child may be subtle.
Regular follow-up, especially of complex cases, is recommended to identify early lesions, especially malignant peripheral nerve sheath tumors.
Neurofibromatosis, type 1 (NF1) is an autosomal-dominant genetic disorder with the defining features of café au lait spots, multiple neurofibromas, and iris Lisch nodules. Additional manifestations are almost always present, including those involving the skin, central nervous system, peripheral nerves, bones, gastrointestinal tract, vasculature, and endocrine system. The most common additional manifestations are learning disabilities; optic pathway gliomas; diffuse, occasionally massive plexiform neurofibromas; dystrophic scoliosis; sphenoid wing dysplasia; renovascular hypertension; and malignant peripheral nerve sheath tumors.
History and exam
Key diagnostic factors
- family history of NF1
- pain, any location
- neurologic deficits: gross motor delay, general incoordination, school performance problems
- compromised vision
- compromised social interactions
- skin: café au lait spots, axillary freckling, cutaneous juvenile xanthogranulomas, neurofibromas
- head and neck: unilateral diffuse plexiform neurofibroma divisions of the trigeminal nerve
- ophthalmologic: visual compromise, optic disk pallor, iris Lisch nodules
- central nervous system: signs of hydrocephalus, brain tumors, and/or cerebellar abnormalities
- peripheral nervous system: palpable mass about neck, brachial plexuses, groin, Hunter canal, or the popliteal fossae
- skeletal: tibial dysplasia or pseudarthrosis, sphenoid wing dysplasia, pectus excavatum or carinatum, genu valgum or varum, ankle valgus, pes planus
- gastrointestinal: severe constipation, obstipation, abdominal pain, gastrointestinal bleeding
- vascular: neurologic problems, abdominal pain (and/or hemorrhage)
- autism spectrum disorder
- vascular: hypertension
- parent with NF1
- severe crush trauma
1st investigations to order
- MRI and/or CT scans
- PET scan
- genetic testing to confirm NF1 mutation
malignant peripheral nerve sheath tumor
- Neurofibromatosis type 2 (NF2)
- McCune-Albright syndrome
- Familial café au lait spots
- Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation
- Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966
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