Fragile X syndrome: an overview

Key content: Fragile X syndrome is the most common hereditary cause of learning difficulty and the most common known cause of autism. It occurs as a result ofmutations of the FMR-1 gene on the X chromosome and it belongs to the family of trinucleotide-repeat disorders. The prevalence of the full genetic mutation is approximately 1 in 4000. The inheritance is X-linked dominant with reduced penetrance and variable expressivity. Premutation carrier status is linked to fragile X tremor ataxia syndrome and premature ovarian failure. Learning objectives: To understand the clinical features and the basic genetics. To understand the nature and implications of premutation carrier status, including the link with premature ovarian failure. To be aware of the complexities of counselling. To be aware of the UK policy on screening. Ethical issues: There are issues about termination of pregnancy in relation to fragile X syndrome and fragile X tremor ataxia syndrome. Carrier testing for fragile X syndrome has potential health implications for the tested individual.