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Neurofibromatosis type 1 Factsheet

Published October 2013 NCHPEGAll rights reserved

Clinical featuresNeurofibromatosis type 1 (NF1) is highly variable hereditary condition involving the skin, nerves, and bone. Common features

include caf au lait spots, axillary and inguinal freckling, ocular manifestations including Lisch nodules and optic glioma, and benign

cutaneous neurofibromas, tumors that can cause disfigurement and organ dysfunction. Learning disabilities are present in 50% of

individuals with NF1. Manifestations vary widely even within a family. Features may range from mild skin findings to multiple

tumors, including malignancies. The lifetime risk for malignancy associated with NF1 is approximately 7%, or ~1 in 14.

Early child development is typically normal and features developing with age. Children present with caf au lait spots congenitally or

within the first years of life; certain less common features such as tibial bowing are congenital. Other features emerge over time,

increasing during puberty and adulthood. Plexiform neurofibromas, optic glioma, and other skeletal abnormalities typically present

in childhood, and cutaneous neurofibromas and Lisch nodules have an average onset in adolescence. Neurofibromas progress into

adulthood, and adults may develop hypertension and malignant nerve sheath tumors.

Diagnosis

Diagnosis is typically based upon clinical features (see checklist on page 2). Most individuals with NF1 can be diagnosed based on

clinical findings by middle to late childhood. Molecular genetic testing can also diagnose NF1 but is usually unnecessary.

Genetics

NF1 is caused by mutations in the NF1 gene. NF1 mutations or deletions/duplications are found in 95% of individuals who have a

clinical diagnosis of NF1. Occasionally mosaic NF1 occurs when an individuals has some cells with an NF1 mutation and others

without the mutation.

Inheritance

NF1 is an autosomal dominant condition with variable expression. Individuals with NF1, even within the same family, can have highly

variable presentations. The children of an individual with NF1 have a 50% chance to inherit the condition. Half of affected individuals

inherited the condition from an affected parent and half of individuals have unaffected parents and a new gene mutation.

Clinical testingThe testing strategy for NF1 is to evaluate the individual clinically and determine if they meet the diagnostic criteria. Most individuals

can be diagnosed by clinical findings and do not require confirmatory genetic testing. Early or confirmatory diagnosis of NF1 by

genetic testing rarely affects management, except perhaps in an infant to guide surveillance for early serious features. When

diagnostic genetic testing is clinically indicated, a multi-step, multi-technique process is used to maximize detection of disease-

causing variants. Testing typically begins with NF1 sequence analysis and will reflex to deletion/duplication testing and/or

microarray.Management

Management of children with NF1 includes screening for vascular, neurologic and ophthalmologic complications and includes

developmental and educational assessment. Surgery may be indicated to remove uncomfortable, disfiguring or symptomatic

neurofibromas, when possible. Neither preventative nor curative treatments are available. Management is often coordinated

through a multi-disciplinary NF clinic.

7/27/2019 Neurofibromatosis Type 1 Factsheet

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Published October 2013 NCHPEGAll rights reserved

NF1 Clinical Checklist

A clinical diagnosis of NF1 is made when 2 or more of the following criteria

are met:

Comment

Six or more caf au lait macules over 5 mm in greatest diameter

in prepubertal individuals and over 15 mm in greatest diameter

in postpubertal individuals

Two or more neurofibromas of any type or one plexiform

neurofibroma

Freckling in the axillary and/or inguinal regions

Optic pathway glioma

Two or more Lisch nodules (iris hamartomas)

A distinctive osseous lesion such as sphenoid dysplasia or tibial

pseudarthrosis

A first-degree relative (parent, sib, or offspring) with NF1 as

defined by the above criteria

References

Childrens Tumor Foundation atwww.ctf.org

Ferner et al. 2007. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet; 44: 81-88.

(Consensus statement from the members of the UK Neurofibromatosis Association Clinical Advisory Board, available at

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598063/)

GeneReviews: Neurofibromatosis 1 athttp://www.ncbi.nlm.nih.gov/books/NBK1109/Genetics Home Reference: Neurofibromatosis type 1 athttp://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1.

National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. 1988. Neurofibromatosis.

1(3):172-8. (http://www.ncbi.nlm.nih.gov/pubmed/3152465)

Viskochil D. (2010). Neurofibromatosis type 1. In S. B. Cassidy, & J. E. Allanson (Eds.), Management of genetic syndromes (3rd

edition,

pp. 549-586). Hoboken, N.J.: John Wiley & Sons, Inc.

http://www.ctf.org/http://www.ctf.org/http://www.ctf.org/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598063/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598063/http://www.ncbi.nlm.nih.gov/books/NBK1109/http://www.ncbi.nlm.nih.gov/books/NBK1109/http://www.ncbi.nlm.nih.gov/books/NBK1109/http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1http://www.ncbi.nlm.nih.gov/pubmed/3152465http://www.ncbi.nlm.nih.gov/pubmed/3152465http://www.ncbi.nlm.nih.gov/pubmed/3152465http://www.ncbi.nlm.nih.gov/pubmed/3152465http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1http://www.ncbi.nlm.nih.gov/books/NBK1109/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598063/http://www.ctf.org/