fragile X syndrome

Fragile X syndrome is the most common cause of inherited developmental delay. It is caused by a recessive gene mutation on the long arm of the X sex chromosome. Some degree of intellectual impairment is present in affected patients, ranging from mild to severe, but usually moderate. Most children with fragile X syndrome suffer from attention problems as well, and may have a variety of other problems including speech disorders, hand mannerisms and autistic behaviors, and emotional problems.

Prevalence in males: 1 in 1,000 to 2,000. Many are learning disabled, others are retarded. About one in 260 women is a carrier. Of these, about 70% of girls carrying the mutation are apparently unaffected. The other 30% may show mild symptoms or may be mentally retarded.

This syndrome should be at least considered in any case of unexplained developmental delay, especially in males. Of course, genetic counselling for the family, both immediate and extended, is crucial. Specific DNA testing is available, and can be given to prospective or pregnant mothers who are concerned based on family history they might carry the mutation.

The syndrome involves a mutation with repetitive duplication of a very short segment of the gene for the protein FMR1, which is apparently critical to normal brain maturation. Increasing numbers of repetitions of a specific short coding sequence within the gene cause the production of a progressively more abnormal protein. That is, roughly speaking, the more repetitions, the more severely affected the individual. Persons with fewer repetitions are carriers who may have mild or no signs of the condition.

This syndrome often goes unidentified by parents and doctors. The syndrome may be especially difficult to diagnose in the first year of life, when signs are minimal. Addtionally, at least half of children with the fragile X syndrome do not show classical physical signs (as listed below).

Fragile X syndrome should be suspected whenever a boy presents with unexplained mental retardation, developmental delay, or behavioral signs such as hand-flapping movements, hyperactivity, attention deficits or autistic like behaviors, especially if there is a family history of similarly affected males. About 15% of fragile X children show varying degrees of autism. Anxiety, obsessive-compulsive behaviors and extreme shyness are common. About 10% of fragile X patients suffer from seizures.

There is no cure for fragile X syndrome, but therapy for children with fragile X is individualized, is aimed at encouraging their strengths and remediating weak areas, and is best started as early in life as possible. Children with fragile X often have specific learning disabilities, and many fragile X children have symptoms of attention deficit and may require medication to function more normally in school.

Physical signs of fragile X (absent in 50% or more of patients) include:

normal height
broad forehead
elongated face
large prominent ears
strabismus
high arched palate
hyperextensible joints ("double-jointed")
hand calluses (from repetitive self-abuse)
pectus excavatum
mitral valve prolapse
enlarged testicles
ow muscle tone (hypotonia)
soft, fleshy skin
flat feet
seizures

Resources for parents with fragile X children or carriers as well as relatives of these children include:

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