Fragile X Syndrome

Fragile X syndrome (FXS), or Martin-Bell syndrome, is a genetic syndrome which results in a spectrum of characteristic physical and intellectual limitations and emotional and behavioral features which range from severe to mild in manifestation.

Frequency
Conservative estimates report that fragile X syndrome affects approximately 1 in 4000 males and 1 in 8000 females.

Pathology
The symptoms of fragile X syndrome are caused by abnormalities in DNA on the X chromosome. Examination of the karyotype reveals a constriction at the end of the long arm of the X chromosome, followed by a thin strand of genetic material. The constriction and thin strand give the appearance of a fragile portion of the X chromosome. Sequencing of the genetic material reveals a repeating base pair triplet that is responsible for the syndrome.

Symptoms and Signs
People with fragile X syndrome have physical, cognitive and behavioral abnormalities. They have large, protuberant ears; a prominent chin and forehead; a high arched palate; and, in postpubertal males, macroorchidism. The joints may be hyperextensible, and heart disease (mitral valve prolapse) may occur. Cognitive abnormalities may include mild to moderate mental retardation. Features of autism may develop, including perseverative speech and behavior, poor eye contact, and social anxiety. Women may experience menopause in their mid-30s.

PHYSICAL PHENOTYPE

• Prominent ears (one or both)
• Long face (vertical maxillary excess)
• High-arched palate (related to the above)
• Hyperextensible finger joints
• Double-jointed thumbs
• Flat feet
• Soft skin
• Larger testes in men
• Low muscle tone.

Diagnosis
Fragile X syndrome is frequently not suspected until school age or adolescence, depending on the severity of the symptoms. Boys with autism and mental retardation should be tested for fragile X syndrome. DNA testing can detect abnormal DNA on the fragile X chromosome. The greater the number of abnormal repetitions of DNA found, the more likely the child will have symptoms.

Treatment
Early intervention, including speech and language therapy and occupational therapy, can help children with fragile X syndrome to maximize their abilities. Stimulants, antidepressants, and antianxiety drugs may be beneficial for some children.