X linked mental retardation and verbal disability

Abstract

Whether based on institutional data or on community surveys, almost all censuses of retarded populations have shown an excess of males. The sex difference in the incidence of mental retardation is not, as far as can be determined, associated with lower average intelligence in males. There is evidence that in addition to the excess of retardates among males there is also a larger number of males at the highest levels of IQ. Such greater variability could be accounted for by the presence of one or more major genes relating to intellectual functioning on the X chromosome. Another line of evidence linking transmission of mental retardation to the X chromosome lies in the study of families in which there is more than 1 retarded person. Several studies show far more sibships than chance alone would explain in which all the retarded individuals are male. Another large study shows that the intellectual level of the mother has far more effect on the incidence of retardation among the children than does that of the father. Both types of evidence are compatible with a hypothesis that major genes associated with intellectual functioning are located on the X chromosome. There are certain families, which appear to be fairly numerous in the population, in which nonspecific X linked mental retardation has been found to exist. No consistent physical or physiologic pathology is known to characterize the affected individuals in these families, but mental defect of varying degrees of severity is seen to have been transmitted from generation to generation in the same pattern as that noted for other X linked traits. Clinical evidence, and to some extent experimental data, strongly suggests that certain aspects of intelligence, as yet poorly defined but generally related to verbal functioning, are associated with genes on the X chromosome. In some cases, the effect of these genes is so great that it leads to frank retardation. This is what is noted in the families with nonspecific X linked mental retardation. In the great majority of cases, however, the expression is less severe. When such milder expression occurs in conjunction with other deleterious genetic factors or unfavorable environment, one would expect retardation of the type commonly called 'cultural familial'. Due to the presence of the X linked factor, such retardation would occur more frequently in males than in females. This, more than the presence of more severe types of X linked pathology, would account for much of the excess of male retardates. Although the data on which the estimates are made are still far from precise, it is quite probable that at least a quarter of all mental retardation is due to X linked factors.