What Is Fragile X?
This genetic condition can affect all facets of a person’s life. While there is no cure, advances in science offer new understanding and therapies. By Rear Adm. Joyce Johnson, D.O.

Advances in genetics and systems biology provide new understanding of existing diseases, as well as recognition of new syndromes. A case in point is what we now know about fragile X, which includes the childhood fragile X syndrome (FXS) and the late-adult fragile X-associated tremor/ataxia syndrome (FXTAS).

Fragile X is a genetic condition. FXS can affect a person’s physical, cognitive, behavioral, sensory, and speech and language systems. FXS is the most common cause of genetically inherited mental retardation. FXTAS is a late-life disease with tremors, and memory and balance problems.

A review of basic genetics helps us understand fragile X. Everyone has 23 pairs of chromosomes, made of genes, with each chromosome pair containing genes from each parent. One chromosome pair determines sex—a female has two X chromosomes and a male has one X (from his mother) and one Y (from his father).

Everyone has the FMR-1 gene. If it has a full mutation, it causes FXS. The mutation involves an increased number of a specific amino acid triplet in the DNA. Within a cell, this mutation prevents production of a specific protein that is needed for neurological development. According to a recent study, about 1 in every 3,600 males has the mutation. Although prevalence in females has been less studied, it is likely that 1 in 4,000 to 1 in 6,000 has the mutation.

The symptoms of FXS often include cognitive problems, ranging from minor learning disabilities to mental retardation, and behavioral issues, including hyperactivity or signs of autism. Physical characteristics may include heart murmur, long face, large ears, and loose connective tissue. Some patients experience seizures.

Among individuals, the combination and severity of features varies. Boys generally are more seriously affected than girls, perhaps because the girl’s second X chromosome provides some protection.

Recently, a physician treating children with fragile X noted that some of their grandfathers developed a neurological syndrome in their 50s or 60s. The men had been healthy with normal or above-average intelligence, but with age, they developed a condition that included intention tremor (shaking when reaching for something), loss of balance (ataxia), and short-term memory problems (dementia). Genetic studies found these men had the FMR-1 pre-mutation. In 2001, this syndrome was named FXTAS. Some women have since been identified with the condition.

Diagnoses of FXS and FXTAS are confirmed with a blood sample for DNA testing. Though there is no specific cure, medication and other therapies can be helpful to children with FXS and their families. Treatment for FXTAS generally is symptomatic. Research for the best treatments is ongoing.