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, although 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 tumours.
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 tumours.
History and exam
Key diagnostic factors
- family history of NF1
- pain, any location
- neurological 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
- ophthalmological: visual compromise, optic disc pallor, iris Lisch nodules
- central nervous system: signs of hydrocephalus, brain tumours, and/or cerebellar abnormalities
- peripheral nervous system: palpable mass about neck, brachial plexuses, groin, Hunter's 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: neurological problems, abdominal pain (and/or haemorrhage)
- 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 tumour
D. Gareth Evans, MD, FRCP
Professor of Medical Genetics and Cancer Epidemiology
School of Medicine
University of Manchester
DGE is an author of several studies referenced in this topic. He receives consultancies from Astrazeneca, Springworks, and Recursion. These may impact on recommendations for MEKi treatment.
Professor D. Gareth Evans would like to gratefully acknowledge Dr Vincent M. Riccardi, a previous contributor to this topic.
VMR is an author of several studies referenced in this topic.
Bruce R. Korf, MD, PhD
Department of Genetics
University of Alabama at Birmingham
BRK declares that he has no competing interests.
Patrick Morrison, MD
Consultant in Clinical Genetics
Department of Medical Genetics
Belfast HSC Trust
PM declares that he has no competing interests.
Edward S. Tobias, BSc (Hons), MBChB, MRCP (UK), PhD
Clinical Senior Lecturer and Honorary Consultant in Medical Genetics
Institute of Medical Genetics
University of Glasgow
EST declares that he has no competing interests.
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