Summary
Definition
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
Diagnostic investigations
1st investigations to order
- MRI and/or CT scans
- PET scan
- biopsy
- genetic testing to confirm NF1 mutation
Treatment algorithm
Contributors
Authors
D. Gareth Evans, MD, FRCP
Professor of Medical Genetics and Cancer Epidemiology
Genomic Medicine
School of Medicine
University of Manchester
Manchester
UK
Disclosures
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.
Acknowledgements
Professor D. Gareth Evans would like to gratefully acknowledge Dr Vincent M. Riccardi, a previous contributor to this topic.
Disclosures
VMR is an author of several studies referenced in this topic.
Peer reviewers
Bruce R. Korf, MD, PhD
Professor
Department of Genetics
University of Alabama at Birmingham
Birmingham
AL
Disclosures
BRK declares that he has no competing interests.
Patrick Morrison, MD
Consultant in Clinical Genetics
Department of Medical Genetics
Belfast HSC Trust
Belfast
UK
Disclosures
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
Yorkhill Hospital
University of Glasgow
Scotland
UK
Disclosures
EST declares that he has no competing interests.
References
Key articles
Riccardi VM. Neurofibromatosis: phenotype, natural history and pathogenesis. 2nd ed. Baltimore, MD: Johns Hopkins University Press; 1992.
National Institutes of Health consensus development conference statement. Bethesda, MD, July 13-15, 1987. Neurofibromatosis. 1988;1(3):172-8.Full text Abstract
Mulvihill JJ, Parry DM, Sherman JL, et al. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis): an update. Ann Intern Med. 1990 Jul 1;113(1):39-52. Abstract
Riccardi VM. Neurofibromatosis: phenotype, natural history and pathogenesis. 2nd ed. Baltimore, MD: Johns Hopkins University Press; 1992.
Rodrigues LO, Batista PB, Goloni-Bertollo EM, et al. Neurofibromatoses: part 1 - diagnosis and differential diagnosis. Arq Neuropsiquiatr. 2014 Mar;72(3):241-50. Abstract
Riccardi VM. Neurofibromatosis: phenotype, natural history and pathogenesis. 2nd ed. Baltimore, MD: Johns Hopkins University Press; 1992.
Messiaen LM, Callens T, Mortier G, et al. Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat. 2000;15(6):541-55. Abstract
National Institutes of Health consensus development conference statement. Bethesda, MD, July 13-15, 1987. Neurofibromatosis. 1988;1(3):172-8.Full text Abstract
Listernick R, Ferner RE, Liu GT, et al. Optic pathway gliomas in neurofibromatosis-1: controversies and recommendations. Ann Neurol. 2007 Mar;61(3):189-98. Abstract
Lammert M, Friedman JM, Kluwe L, et al. Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol. 2005;141:71-4.Full text Abstract
Evans DG, Baser ME, McGaughran J, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002 May;39(5):311-4. Abstract
Reference articles
A full list of sources referenced in this topic is available here.
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