Neurofibromatosis type 1 Factsheet

Clinical features
Neurofibromatosis 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 testing
The 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 diseasecausing 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.

Published October 2013 NCHPEG All rights reserved

NF1 Clinical Checklist

A clinical diagnosis of NF1 is made when 2 or more of the following criteria are met: 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 Comment

References
Childrens Tumor Foundation at www.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 at http://www.ncbi.nlm.nih.gov/books/NBK1109/ Genetics Home Reference: Neurofibromatosis type 1 at http://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) rd Viskochil D. (2010). Neurofibromatosis type 1. In S. B. Cassidy, & J. E. Allanson (Eds.), Management of genetic syndromes (3 edition, pp. 549-586). Hoboken, N.J.: John Wiley & Sons, Inc.

Published October 2013 NCHPEG All rights reserved