Genetic Causes of Intellectual Disabilities: Fragile X Syndrome

Fragile X syndrome is the second leading genetic cause of intellectual disabilities (ID, formerly mental retardation). However, it is the leading genetic cause in males. It involves a genetic anomaly of the FRM1 gene. This is located on the X (sex-determining) chromosome. This gene normally occurs as multiple copies. However, with Fragile X, the code is repeated in excess. People can be carriers of Fragile X without any symptoms. In other words, family members may have excessive repeats of the gene. However, the repeats are not enough to cause ID. Fewer repeats mean fewer problems.

Fragile X is the most common genetic cause of intellectual disabilities in males. If females have a working copy of the FRM1 gene, the abnormal copy is not expressed. Even so, Fragile X remains a significant cause of ID in both females and males.

There are several physical features of Fragile X. The face is elongated and the ears are large. The forehead tends to be larger than normal. The jaw has a pronounced shape. People with Fragile X are generally large in stature, but with poor muscle tone. Males tend to have abnormally large testicles. This becomes evident during adolescence.

Behavioral features include a reluctance to make eye contact. They may engage in odd, stereotyped movements. Other behavioral traits include hyperactivity, tremors, and poor coordination. Their social and communication skills are not well developed. They tend to be withdrawn and shy. Similar behavioral symptoms are characteristic of autism. People can receive a diagnosis of both ID and autism. There are three subtypes of Fragile X. The first is easily detected. It is expressed at birth. The cognitive deficits are more severe. This type is shares many symptoms of autism. This includes social avoidance, repetitive movements, and severe delays in speech and language.

A second type of Fragile X affects a person's sense of balance. They also have tremors and memory deficits.

The third type is Fragile X-related Premature Ovarian Failure (POF). It is limited to females. The ovaries do not function correctly. This leads to infertility and early menopause.