Neurofibromatosis type 1
- Neurofibromatosis (NF) is the collective name for a group of conditions that predispose to both benign and malignant tumours of the central nervous system. The two most common types are known as NF1 and NF2, and are two quite separate conditions.
- NF1, formerly known as Von Recklinghausen disease, is an inherited multisystem disorder that most 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 when several members of the same family are affected (variable expression).
- NF1 is an autosomal dominant condition caused by a mutation in the neurofibromin (NF1) gene on chromosome 17.
- NF1 is one of the most common inherited conditions, with a prevalence of 1 in 3,000 individuals.
- The diagnosis of NF1 is made on clinical grounds, following internationally agreed criteria.
- Many people diagnosed with NF1 never experience health problems, but about one-third will have medical problems related to the disorder at some point in their life. These include hypertension, ophthalmic, orthopaedic and dermatological problems, tumours and problems of self-image. Of these, many are mild and easily treatable, but others are 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.
The diagnosis of NF1 is made on clinical findings. Strict diagnostic criteria have been established and should always be used when 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 greatest diameter 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; and/or
- 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 four years of age; DNA testing is only infrequently needed for diagnosis.
- 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 new mutation.
- NF1 is caused by mutations in the neurofibromin (NF1) gene. More than 500 mutations have been described, with no common mutation existing in any population. DNA testing by direct mutation detection is available, but is very complicated owing to the large size of the gene and is usually reserved for very specific clinical situations. The mutation detection rate approaches 90%.
- 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 personal medical history with particular attention to features of NF1, a physical examination with particular attention to the skin, skeleton, cardiovascular system and neurological systems, ophthalmologic evaluation including slit lamp examination and developmental 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 and with the condition, comprising regular blood pressure monitoring, annual ophthalmologic examination (including visual fields) in early childhood, with less frequent examination in older children and adults, and regular developmental and growth assessment during childhood. Further investigations as indicated.
- For those with complex symptomatology, a multidisciplinary approach to management in a specialist clinic is advised.
Genetic testing can be used to:
- confirm the diagnosis in someone with possible neurofibromatosis type 1 (diagnostic testing), though this is rarely needed; and
- 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.
This information is intended for educational use and was current in August 2013. For clinical management, it is recommended that local guidelines and protocols are used.