About Fragile X Syndrome
What is fragile x syndrome?Fragile X Syndrome (FXS) is a genetic disorder caused by a mutation (a change in the DNA structure) in the X chromosome. It is the most common known cause of inherited developmental disability worldwide.
How common is it?One in 2,500 males and one in 5,000 females are affected. One in 250 females carry the premutation and will pass the gene on to 50% of their offspring, male or female. What is the cause?The genetic disorder is a mutation (change in the DNA structure) in a gene on the ‘X’ chromosome called FMR1 (fragile X mental retardation gene 1). This gene normally contains a repeat code of 6 – 50 ‘CGG’ triplet repeats. Premutation carriers have a small change in the FMR1 gene (a repeat code of 50 –200), whereas the full mutation tend to be affected individuals with a large change in the gene (more than 200 repeats). The mutation turns the gene off, thus causing the problems associated with the syndrome. The clinical features of Fragile X Syndrome range from normal through mild to severe in presentation. What are the clinical features?PhysicalBoys and girls may have prominent ears, high forehead, high palate, hyper-flexible joints, soft skin and flat feet. After puberty, the face may gradually become longer and boys may develop testicular enlargement. Medical complications do not generally develop, however, ear infections are common and there is an increased risk of epilepsy (seizures), strabismus (squint), mitral valve prolapse, hernia and joint dislocations. Physical features may not always be present, especially in children. Developmental Intellectual disability occurs in 80% of males and 65% of females. Global problems tend to occur with learning disabilities and delays in speech, fine and gross motor movements and co-ordination difficulties. Behavioural and emotional Common features include attention deficit disorders with or without hyperactivity, anxiety (hyperarousal), extreme reaction or aversion to sensory stimuli (loud noise, touch, strong smells or tastes, eye contact) and difficulties with expressive language. Autism-like features include hand flapping and biting (or chewing on clothes), poor eye contact and resistance to changes in routine. A diagnosis of autism spectrum disorder, pervasive developmental delay or Aspergers may have been made. Girls may appear less affected and may present with shyness, social anxiety and moodiness. A note on carriers: A sub-group of carriers of the premutation may exhibit mild features of the full mutation including learning or emotional difficulties. There is a higher risk of early menopause in females and older males may develop a neurological disorder with hand tremour and balance problems. How is it diagnosed?Families should visit their GP for referral to a geneticist or developmental paediatrician who can then arrange for a simple blood test. The test to request is “DNA studies for fragile X syndrome” although cytogenetic studies (“karyotyping”) should also be performed to exclude other genetic disorders. Testing should be done in combination with genetic and supportive counselling. Who should be tested?Testing should be considered for:
Early detection allows the implementation of effective treatment and intervention strategies thus optimising outcome. As this is an inherited condition, diagnosis also allows families to make informed choices regarding both treatment and family planning. Weaknesses
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