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Fragile X Syndrome

By

Nina N. Powell-Hamilton

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Last full review/revision Jun 2020| Content last modified Jun 2020
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Fragile X syndrome is a genetic abnormality on the X chromosome that leads to intellectual disability and behavioral disorders. Diagnosis is with molecular DNA analysis. Treatment is supportive.

Fragile X syndrome is the most common inherited cause of intellectual disability, with males being more commonly affected than females. (Down syndrome Down Syndrome (Trisomy 21) Down syndrome is an anomaly of chromosome 21 that can cause intellectual disability, microcephaly, short stature, and characteristic facies. Diagnosis is suggested by physical anomalies and... read more Down Syndrome (Trisomy 21) is the most common cause of intellectual disability in males; although it is a genetic disorder, most cases occur sporadically and are not inherited.) For more information, see the National Fragile X Foundation.

The symptoms of Fragile X syndrome are caused by an abnormality of the FMR1 gene on the X chromosome. The abnormality is an unstable triplet repeat expansion; unaffected people have < 54 CGG repeats and people with Fragile X syndrome have > 200. People with 55 to 200 CGG repeats are considered to have a premutation because the increased number of repeats increases the likelihood that further mutation will result in > 200 repeats in a subsequent generation.

Fragile X syndrome affects about 1/4000 males and 1/8000 females. The premutation is more common. Females with the disorder are typically less impaired than males. Fragile X is inherited in an X-linked pattern and does not always cause clinical symptoms in females.

In the past, examination of the karyotype revealed a constriction at the end of the long arm of the X chromosome, followed by a thin strand of genetic material, which was why the syndrome was considered a chromosomal anomaly. However, this structural defect does not appear when modern cytogenetic techniques are used, and this is the reason why Fragile X syndrome is now considered a single-gene disorder and not a chromosomal anomaly.

Symptoms and Signs of Fragile X Syndrome

People with Fragile X syndrome may have physical, cognitive, and behavioral abnormalities. Typical features include 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 Mitral Valve Prolapse (MVP) Mitral valve prolapse (MVP) is a billowing of mitral valve leaflets into the left atrium during systole. The most common cause is idiopathic myxomatous degeneration. MVP is usually benign, but... read more Mitral Valve Prolapse (MVP) ) may occur.

Cognitive abnormalities may include mild to moderate intellectual disability. Features of autism may develop, including perseverative speech and behavior, poor eye contact, and social anxiety.

Women with the premutation may have premature ovarian failure; sometimes menopause occurs in the mid-30s. Males and females with an FMR1 premutation are at risk of Fragile X–associated tremor/ataxia syndrome Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS) Fragile X–associated tremor/ataxia syndrome is a genetic disorder affecting mostly men and causing tremor, ataxia, and dementia. Tremor is a common early symptom that is followed by ataxia,... read more (FXTAS), which is associated with gait abnormalities, intention tremors, later intellectual impairment, and psychiatric problems.

Diagnosis of Fragile X Syndrome

Treatment of Fragile X Syndrome

  • Supportive measures

Early intervention, including speech and language therapy and occupational therapy, can help children with Fragile X syndrome maximize their abilities.

Stimulants, antidepressants, and antianxiety drugs may be beneficial for some children.

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

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