Fragile Syndrome X

Fragile X syndrome is an inherited disorder caused by a trinucleotide repeat expansion of DNA on the X chromosome. This expansion results in the absence or severe deficiency of the FMR1 protein (FMRP), which is known to be essential for normal brain function. FMRP appears to have an RNA-binding activity and may play an important role in synaptic maturation. Approximately 1 per 4,000 males and 1 per 6,000 females are affected. Males with Fragile X syndrome typically have moderate to severe mental retardation, which may be accompanied by hyperarousal or autisticlike behavior. Physical features include large ears, large testicles, and loose connective tissue. Females are more mildly affected; about one-third develop normally, one-third exhibit mild learning disabilities, and one-third have mild mental retardation. Carriers, approximately 1 per 260 women, are typically unaffected, and the risk of expansion to the full disorder increases with successive generations. Identification using DNA analysis of blood is highly accurate but must be specifically requested, and thus many cases go undiagnosed.