Fragile X Disorders

Fragile X Syndrome

Background and Prevalence

Fragile X syndrome (FXS) is the most common known cause of inherited intellectual disability. Estimated frequencies of fragile x syndrome (full mutation carriers) are approximately 1:7,000 males and 1:11,000 females, with frequencies of individuals carrying the premutation are approximately 1:850 males and 1:300 females.

Cause

A diagnosis of Fragile X syndrome is confirmed when there are >200 CGG repeats (“full mutation”) in the FMR1 gene. This large expansion turns off the gene so no protein (FMRP) is produced. The absence of the protein causes Fragile X syndrome.

Symptoms

Because the FMR1 gene is on the X chromosome (one of the two chromosomes that determine a person's sex), males and females may be affected differently although both may demonstrate early delays in speech and motor development. Males with Fragile X Syndrome have cognitive disabilities, ranging from learning disabilities to intellectual disability. Characteristic physical and medical features of fragile x in males include a long face, prominent ears and chin, arched palate, large testicles at puberty, low muscle tone, flat feet, hyperextensible joints, sleep problems, seizures, recurrent ear infections, and mitral valve prolapse. Males with FXS tend to exhibit behaviors of hyperactivity, short attention span, hand biting or hand flapping, poor eye contact and social skills, shyness, anxiety, delayed speech and motor development, repetitive speech, and sensitivity to sensory stimulation (including a hypersensitivity to being touched). Approximately 25-40% of boys with FXS are diagnosed with autism.

Because females have two X chromosomes, one of which typically with a normal FMR1 gene, females tend to have less significant cognitive, physical, and behavioral symptoms of FXS. About 30% of females with the full mutation have IQ scores in the normal range. These individuals generally experience mild learning disabilities or no discernable mental impairment. The remaining 70% of females with FXS have IQ scores falling below the average range of scores. Most experience borderline or mild intellectual. As with males, physical features such as long face, prominent ears, and arched palate are common yet variable among females with the full mutation of the FMR1 gene. Although females with FXS also tend to have some difficulty with attention and concentration, they are less likely than males to exhibit hyperactivity. Females also are less likely to have symptoms similar to those seen in autism. However, shyness, poor social skills, sensory sensitivities, anxiety, and depression are common among females with the full mutation.

Treatment

Although many targeted treatments are being investigated in clinical trials, there is no known cure for FXS. However, a variety of clinical treatments and interventions are available to address specific symptoms common among individuals with the disorder. Treatment often involves medication and behavioral therapy as well as speech and occupational therapy to address delays in language and motor development. Several web sites, including the National Fragile X Foundation (www.fragilex.org) provide information about the treatment of FXS.

Caregivers

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