Neurofibromatosis type 1 - NHS National Genetics Education and ...

Genetic conditions seriesNational Genetics and GenomicsEducation CentreNeurofibromatosis type 1Facts about neurofibromatosis type 1• Neurofibromatosis (NF) is the collective name for a group of conditions which predispose toboth benign and malignant tumours of the central nervous system. The two most commontypes are known as NF1 and NF2 and are two quite separate conditions. This fact sheet is onlyabout NF1.• NF1, formerly known as Von Recklinghausen disease is an inherited multi-system disorder whichmost commonly presents with multiple café-au-lait, patches (brown coffee coloured skin marks).• The condition is extremely variable and it is impossible to predict the phenotype even whenseveral members of the same family are affected (variable expression).• NF1 is an autosomal dominant condition caused by a mutation in the neurofibromin (NF1) geneon chromosome 17.• NF1 is one of the most common inherited conditions, with a prevalence of 1 in 3000 individuals.Clinical features• The diagnosis of NF1 is made on clinical grounds, following internationally agreed criteria.• Many people diagnosed with NF1 never experience health problems but about a third will have medical problemsrelated to the disorder at some point in their life. These include hypertension, ophthalmic, orthopaedic anddermatological problems, tumours and problems of self image. Of these many are mild and easily treatable, but othersare more severe.• About half the individuals with NF1 have a learning disability, although this is usually mild.• Once the diagnosis is made it is important to instigate surveillance for some of the complications that may occur (seebelow).DiagnosisThe diagnosis of NF1 is made on clinical findings. Strict diagnostic criteria have been established and should always be usedwhen assessing individuals. An individual with NF1 has two or more of the following features:• Six or more cafè au lait macules over 5mm in greatest diameter in prepubertal individuals and over 15mm in greatestdiameter in postpubertal individuals• Two or more neurofibromas of any type or one plexiform neurofibroma• Freckling in the axillary or inguinal regions• Optic glioma• Two or more Lisch nodules (iris hamartomas)• A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis• A first-degree relative (parent, sibling or child) with NF1 as defined by the above criteria.Using these criteria a definitive diagnosis can be made in most children by 4 years of age; DNA testing is only infrequentlyneeded for diagnosis.Genetic basis• NF1 is an autosomal dominant condition, with extremely variable expression. Each child of someone with NF1 has a 50%or 1 in 2 chance of inheriting the gene alteration that causes the condition.• About 50% of individuals with NF1 have an affected parent, the remaining 50% have the condition as the result of a newmutation.• NF1 is caused by mutations in the neurofibromin (NF1) gene. More than 500 mutations have been described, nocommon mutation existing in any population. DNA testing by direct mutation detection is available but is veryThis sheet may be photocopied for non-commercial education purposes for healthcare staff© 2012 NHS National Genetics Education and Development Centre (08/12)Genetics and genomics for healthcarewww.geneticseducation.nhs.uk

National Genetics and GenomicsEducation Centrecomplicated due to the large size of the gene and is usually reserved for very specific clinical situations. The mutationdetection rate approaches 90%.Clinical management• The variability of the condition means that each affected individual needs to be assessed on an individual basis.• Once the diagnosis is confirmed an affected individual should have a thorough initial assessment to include a personalmedical history with particular attention to features of NF1, a physical examination with particular attention to the skin,skeleton, cardiovascular system & neurological systems, ophthalmologic evaluation including slit lamp examination anddevelopmental assessment in children. Further investigations may be indicated following this initial assessment.• Ongoing surveillance should include annual physical examination by a physician who is familiar with the individual andwith the condition, comprising regular blood pressure monitoring, annual ophthalmologic examination (including visualfields) in early childhood, with less frequent examination in older children and adults, and regular developmental andgrowth assessment during childhood. Further investigations as indicated.• For those with complex symptomatology a multi-disciplinary approach to management in a specialist clinic is advised.Genetic testingGenetic testing can be used:• to confirm the diagnosis in someone with possible neurofibromatosis type 1 (diagnostic testing), though this is rarelyneeded• to offer prenatal genetic diagnosis, though this is rarely requested.Genetic testing is available across the UK and usually provided through specialist clinics or regional genetic centres.ReferencesFerner, RE. Huson, SM. Thomas, N. et al. Guidelines for the diagnosis and management of individuals withneurofibromatosis 1 PubMed http://www.ncbi.nlm.nih.gov/pubmed/17105749/This information is intended for educational use and was current in July 2012. For clinical management, it is recommended that local guidelines andprotocols are used.This sheet may be photocopied for non-commercial education purposes for healthcare staff© 2012 NHS National Genetics Education and Development Centre (08/12)Genetics and genomics for healthcarewww.geneticseducation.nhs.uk