Birth Defects

Fragile X syndrome is the most common cause of inherited mental retardation, occurring in one out of 1,000 births. It is caused by expansion of a "triplet repeat" section of nucleotides in the FMR-1 gene on the X chromosome. Triplet repeats are three-base-pair sequences in a gene that are abnormally repeated, sometimes dozens or even hundreds of times, causing abnormal protein sequence and structure. Because it is carried on the X chromosome, it affects males more often than females. In males, an FMR-1 gene with greater than 200 repeats is always associated with the syndrome. Inactivated FMR-1 gene causes impaired mental function. The FMR-1 protein is thought to help shape the connections between neurons that underlie learning and memory. Affected individuals may also have large testes, abnormal facial features, seizures, and emotional and behavior problems. DNA testing allows for detection of carriers as well as affected individuals, enabling the use of genetic counseling and prenatal testing.

Another common functional genetic disorder is hearing loss, which can result from a defect in any one of more than fifty different genes. One gene, connexin 26, may be responsible for a large portion of inherited hearing loss. Some forms of congenital hearing loss may be due to prenatal exposure to infectious agents such as rubella. Genetic screening or screening for hearing loss at birth may be the most important test for hearing impairment yet to be developed, as early recognition and treatment can lead to dramatic improvements in hearing and, consequently, in the development of language in early childhood.

Other genetic disorders that cause functional birth defects include those involved in various aspects of the immune system. The most severe form Figure 1. The threshold model for multifactorial traits. The vertical axis represents the number of people with a given level of overall liability. On the horizontal axis, individuals below the threshold do not have the disease, while those above it do. is severe combined immune deficiency (SCID), in which a major type of immune cell, the lymphocyte, is absent. People with SCID suffer life-threatening infections beginning in infancy and may require complete physical isolation. This was the case for David Vetter, who became known to the world as the "bubble boy."