Fragile-X Syndrome: Variability of Phenotypic Expression

Fragile-X syndrome is a recently described X-linked disorder that ranks second to Down syndrome as the most prevalent chromosomal form of mental retardation. Affected male individuals manifest a variable clinical phenotype that includes distinctive facial features, macroorchidism, cognitive and language impairments, and an impressive prevalence of attention deficit disorder and infantile autism. A sizable proportion of female carriers are similarly affected. The molecular basis for these phenotypic features has not been established, nor have the factors mediating the variable expression of the syndrome in vulnerable individuals. However, improved behavioral functioning in prepubertal children may result from early identification and folate supplementation.