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Neurofibromatosis Type 1 - Description

Page Contents

Other Names

NF1, von Recklinghausen's disease

ICD-9

237.7, Neurofibromatosis

For additional ICD-9 codes of related conditions, see NF1 ICD9 (PDF Document 54 KB) .

Description

Neurofibromatosis type 1 (NF1) is a common autosomal dominant neurocutaneous genetic disorder, first described in the medical literature in 1882 and previously known as von Recklinghausen disease. The NF1 gene product, neurofibromin is a Ras-GAP protein and acts as a "tumor suppressor." Mutations in this gene, located on the long arm of chromosome 17, typically inactivate neurofibromin and lead to the tumor phenotype seen in NF1 (reviewed in [Viskochil: 2010]).

In up to 95% of cases, the diagnosis can be made through straightforward clinical evaluation by the time a child is 11 years of age. [Friedman: 1997] Hallmark findings of NF1 include:
  • café-au-lait macules
  • neurofibromas (benign tumors that arise from the nerve sheath, and typically composed of Schwann cells, fibroblasts, mast cells, and pericytes)
  • axillary or groin freckling
  • optic pathway tumors
  • Lisch nodules (benign hamartomas of the iris)
  • dyplastic skeletal findings (long bone bowing/pseudoarthrosis and/or sphenoid wing dysplasia)
  • learning disabilities (in greater than 50% of individuals [Jett: 2010]) and behavioral abnormalities, including autistic features

Genetics

NF1 is caused by mutations in the NF1 gene, which is located at 17q11.2. Many different mutations in the gene have been found, but the type of mutation doesn't correlate with a specific phenotype. For more information, see [Viskochil: 2002]. Within any one family, affected members may display significantly different clinical manifestations. Modifying factors have been suggested but are not well understood. [Szudek: 2002]

NF1 is an autosomal dominant condition. Although the spontaneous mutation rate for the NF1 gene may be as high as 50% [Kandt: 2003], parents and siblings of children with NF1 should be evaluated for signs of NF1. [Jones: 1997] NF1 is fully penetrant in adults with variable age-dependent onset of manifestations.

In adults, NF1 can be diagnosed with relative certainty on a clinical basis and thus rarely requires mutation analysis. All individuals, including adults, suspected of having NF1 should be evaluated by a trained clinical geneticist. However, older individuals with only pigmentary manifestations of NF1 may have a different condition (e.g. Legius syndrome) and, in such cases, NF1 mutation analysis can be helpful in clarifying the diagnosis. DNA testing is clinically available – for information on available gene testing, see [Friedman: 2002].

Prognosis

As features vary considerably in individuals with NF1, prognosis will also vary. However, overall, the average life expectancy of individuals with NF1 is probably 10-15 years shorter than the general population. Malignancy is the most common cause of death, although still rare, including brain tumors and malignant peripheral nerve sheath tumors. [Rasmussen: 2000] [Tonsgard: 2006]

Prevalence

The reported prevalence of NF1 varies from study to study, but a general estimate of the prevalence is approximately 1/3000. [Rasmussen: 2000] NF1 affects individuals without predilection to ethnicity or gender.

Pearls And Alerts

On Initial Diagnosis Page

Older individuals with only pigmentary findings

Segmental NF1

On Ongoing Assessment Page

Gliomas

On Treatment And Management Page

Height

Helpful Articles

PubMed search for articles on Neurofibromatosis Type 1 in children for the last 3 years

Payne JM, Moharir MD, Webster R, North KN.
Brain structure and function in neurofibromatosis type 1: current concepts and future directions.
J Neurol Neurosurg Psychiatry. 2010;81(3):304-9. PubMed abstract

Elefteriou F, Kolanczyk M, Schindeler A, Viskochil DH, Hock JM, Schorry EK, Crawford AH, Friedman JM, Little D, Peltonen J, Carey JC, Feldman D, Yu X, Armstrong L, Birch P, Kendler DL, Mundlos S, Yang FC, Agiostratidou G, Hunter-Schaedle K, Stevenson DA.
Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options.
Am J Med Genet A. 2009;149A(10):2327-38. PubMed abstract

Neurofibromatosis Type 1 Module Authors

Author: David Stevenson MD, 10/2010
Reviewing Authors: David Viskochil MD, PhD, 11/2004
Karin Dent MS, CGC, 1/2004
Content Last Updated: 10/2010

The authors listed above are responsible for the overall Neurofibromatosis Type 1 Module. Authors contributing to individual pages in the module are listed on those pages.

Page Bibliography

Friedman JM.
Neurofibromatosis 1.
Copyright, University of Washington, Seattle. 1997-2004; (2002) http://www.geneclinics.org/servlet/access?db=geneclinics&site=gt&id=88.... In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Available at http://www.genetests.org/. Accessed on 8/14/04.
A concise and well organized review of NF1 with a focus on gene testing.

Friedman JM, Birch PH.
Type 1 neurofibromatosis: a descriptive analysis of the disorder in 1,728 patients.
Am J Med Genet. 1997;70(2):138-143. PubMed abstract
A large case series utilizing an international database; authors are international authorities on clinical aspects of NF1. Excellent review, focused on clinical characteristics and natural history.

Jett K, Friedman JM.
Clinical and genetic aspects of neurofibromatosis 1.
Genet Med. 2010;12(1):1-11. PubMed abstract

Jones KL.
Smith's Recognizable Patterns of Human Malformation.
5th ed. Philadelphia: W. B. Saunders Company; 1997. 0721661157
Concise reviews of syndromes with an emphasis on dysmorphology. Syndromes described in sections broken down into abnormalities, natural history, and etiology.

Kandt RS.
Tuberous sclerosis complex and neurofibromatosis type 1: the two most common neurocutaneous diseases.
Neurol Clin. 2003;21(4):983-1004. PubMed abstract

Rasmussen SA, Friedman JM.
NF1 gene and neurofibromatosis 1.
Am J Epidemiol. 2000;151(1):33-40. PubMed abstract

Szudek J, Joe H, Friedman JM.
Analysis of intrafamilial phenotypic variation in neurofibromatosis 1 (NF1).
Genet Epidemiol. 2002;23(2):150-64. PubMed abstract

Tonsgard JH.
Clinical manifestations and management of neurofibromatosis type 1.
Semin Pediatr Neurol. 2006;13(1):2-7. PubMed abstract

Viskochil D.
Genetics of neurofibromatosis 1 and the NF1 gene.
J Child Neurol. 2002;17(8):562-70; 571-2, 646-51. PubMed abstract

Viskochil DH.
Neurofibromatosis Type 1.
Management of Genetic Syndromes, 3rd Edition. 2010; 549-568. New York: Wiley-Blackwell; http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Excellent review of NF1 by an expert in the field. Book is a great resource for Medical Home providers, with chapters on 25 different genetic conditions.