Fragile X Syndrome

What Is It?

Fragile X syndrome is an inherited disorder associated with mental retardation and a particular appearance. It results from an error in a small piece of the DNA (genetic blueprint) for the FMR-1 gene. This gene is found on the X chromosome, one of the two chromosomes, X and Y, that determine gender.

In people with fragile X, a particular section of the DNA code — CGG — is "fragile" and gets repeated an unusually large number of times (compared with the normal five to 50 times). As a result, the FMR-1 gene is not expressed ("turned on"), and the body cannot produce FMR-1 protein, which is related to nerve function.

Depending on the number of CGG repetitions, fragile X can have a variety of physical, intellectual and behavioral effects. People with more repetitions tend to have more severe symptoms. For example, people with 200 or more CGG repetitions are described as having a full fragile X mutation and usually develop many of the symptoms of fragile X syndrome, including mental retardation. People with 50 to 200 CGG repetitions are described as having a fragile X premutation and may not show any obvious signs or symptoms of fragile X syndrome. The number of CGG repetitions can increase when the gene is passed from generation to generation, increasing the chance of developing the full fragile X mutation.

Fragile X syndrome is seen in approximately one in 1,200 males and one in 2,500 females. However, many more people carry the fragile X gene, either the full mutation or the premutation, but show no signs or symptoms of the syndrome. Fragile X syndrome is the most common inherited cause of mental retardation in males.

Symptoms

Signs and symptoms vary and can include:

• Elongated face, large, protuberant ears, prominent chin and forehead, large testicles in boys (especially after puberty)
• Other physical problems, including cleft palate, strabismus (crossed eyes), serous otitis media (middle-ear fluid that is not infected), dislocated hips, unusually flexible joints (being double-jointed), club feet, seizures and mitral-valve prolapse
• Cognitive and intellectual problems, including mental retardation, learning disabilities and abnormal speech
• Behavioral problems, including hyperactivity, attention difficulties, avoidance of eye contact, violent outbursts (especially in teen-age boys) and an unusual hypersensitivity to environmental stimuli such as sights, sounds, smells and touch

Fragile X tends to be milder and less obvious in females. A female normally inherits two X chromosomes, one from each parent. If one of the X chromosomes has the fragile X mutation, the other X chromosome, inherited from her unaffected parent, can partially compensate for the incorrect genetic information. About half of affected females show no symptoms of fragile X syndrome. The other half have symptoms, especially learning disabilities, behavioral problems or intellectual impairment.