Clinical features: Fragile X syndrome is the commonest cause of inherited learning disability after Down syndrome. It is characterised by moderate to severe mental retardation in affected males and mild mental retardation in affected females. Affected males have a characteristic appearance with large head, long face, prominent forehead and chin, large protruding ears and large testes postpubertally. Behavioural problems including autistic spectrum disorder are common.
Incidence: Approximately 1 in 4,000 ? 1 in 6,000.
Inheritance : X-linked dominant, but the pattern of inheritance can be complex because of the nature of the mutation which causes the condition (see below).
Gene: Fragile X syndrome is caused by a mutation in the fragile X mental retardation 1 gene (FMR1) on the X chromosome.
The mutation in fragile X syndrome is an amplified CGG triplet (trinucleotide) repeat. In people who do not have fragile X syndrome there are between 6 and 45 copies of the CGG triplet repeat within the gene. Individuals with 55 ? 200 of these repeats are healthy but are said to have the premutation. People with the full mutation have more than 200 CGG repeats and will show features of fragile X syndrome. This means that there is also a grey or intermediate zone of 46 ? 54 repeats, which can be difficult to interpret. In individuals with the premutation, the FMR1 gene is unstable and there becomes a high probability that the CGG repeat number will increase in the next generation to a full mutation. All males with the full mutation will have fragile X syndrome. Approximately 50% of females with the full mutation will have symptoms of fragile X syndrome but in general, learning disability is much less severe than in males with the condition. People with a premutation are usually not affected by fragile X syndrome. However, it is now recognised that approximately 20% of women with an FMR1 premutation experience premature ovarian failure and some older males with the premutation develop a progressive cerebellar ataxia and intention tremor.
Prenatal diagnosis: Yes. Please refer to your local clinical genetics service prior to a pregnancy. This ensures family members are offered appropriate advice and investigations, to confirm whether or not prenatal diagnosis is possible.
Carrier testing: Yes.
UK Support Group: Fragile X Society Rood End House 6 Stortford Road Grean Dunmow Essex CM6 1DA Tel: 01371 875 100 Web: www.fragilex.org.uk
If you would like further information on fragile X syndrome please go to either:-
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