Mental retardation: genetic findings, clinical implications and research agenda

The most important genetic advances in the field of mental retardation include the discovery of the novel genetic mechanism responsible for the Fragile X syndrome, and the imprinting involved in the Prader-Willi and Angelman syndromes, but there have also been advances in our understanding of the pathogenesis of Down syndrome and phenylketonuria. Genetic defects (both single gene Mendelizing disorders and cytogenetic abnormalities) are involved in a substantial proportion of cases of mild as well as severe mental retardation, indicating that the previous equating of severe mental retardation with pathology, and of mild retardation with normal variation, is a misleading over-simplication. Within the group in which no pathological cause can be detected, behaviour genetic studies indicate that genetic influences are important, but that their interplay with environmental factors, which are also important, is at present poorly understood. Research into the joint action of genetic and environmental influences in this group will be an important research area in the future.