Fragile X Syndrome

Definition

Fragile X syndrome is an X chromosome defect that causes mental retardation and a wide range of associated signs and symptoms.

Description

This syndrome is the second most common identifiable cause of genetic mental retardation after Down syndrome. It was first identified by geneticist Herbert Lubs, who observed the chromosomal defect responsible for the syndrome in 1969.

Some people have chromosomes that when studied in a laboratory, have a tendency to "break" or "tear." The damage to these aberrant chromosomes typically occurs in particular regions, called fragile sites.

Most of the time these fragile sites are not associated with medical problems, but a pronounced gap in one such region, at the end of the long arm of the X chromosome is associated with fragile X syndrome.

For unexplained reasons, fragile X syndrome does not behave in the typical manner of an X-linked trait. Nearly 20 percent of fragile X males are silent carriers, who are unaffected by the syndrome but can pass the fragile X chromosome to their female offspring. About one-third of female fragile X carriers, who would be expected to be asymptomatic, exhibit some symptoms of the disorder.

Since the late 19th century it has been noted that males institutionalized for mental retardation outnumber females by five to four. The fragile X syndrome and other forms of X-linked mental retardation account for part of the difference.

Fragile X syndrome is estimated to affect one in 2,000 males and to be responsible for 10 percent of mentally retarded males. It has been described in whites, blacks, Indians, Filipinos, Japanese, and Zulus.

Symptoms

In addition to moderate to severe mental retardation, other characteristics of individuals with fragile X syndrome may include large ears, large testes (macroorchidism), large jaw (prognathism), speech delays, prominent forehead, double-jointedness, autistic symptoms and occasional self-mutilation.

The face is typically long and narrow, and a high arched palate, large ears, otitis media, strabismus, and dental problems are present.

Other common characteristics include hyperextensible joints, hypotonia, and heart problems including mitral valve prolapse. In males, abnormally large testes are a distinctive feature.

In young children, delayed motor development, hyperactivity, behavioral problems, toe walking, and occasional seizures can occur. Autism is suggested by poor eye contact, hand flapping, hand biting, and self-stimulating behaviors.

Poor sensory skills and mathematical ability are sometimes found in conjunction with good reading skills. Speech and language problems can include echolia, perseveration, poor language content, and cluttering (dropping of letters or syllables when speaking).

Affected girls tend to be shy and socially withdrawn, and to have particular difficulty with mathematics.

Treatment

Standard treatment includes special education, speech, occupational, and sensory integration training; and behavior modification programs. Surgical correction of heart defects is sometimes necessary. Genetic counseling will benefit families of affected persons. Other treatment is symptomatic and supportive.

Folic acid has been found to improve hyperactivity and attention deficits in some pre-adolescent males with fragile X syndrome.

Questions to Ask Your Doctor

Does the child have a chromosome defect?

Is it fragile X syndrome?

What degree of mental retardation is present?

What are the associated physical problems?

How can these physical problems be treated?

What are the developmental problems?

What can be done about these developmental problems?

Will special education or speech training help?

Will folic acid be beneficial?