A biologic and genetic study of 40 cases of severe pure mental retardation.

The family history of 40 patients with severe "pure" mental retardation (MR) was studied to determine the incidence of mental retardation and dull-normal intelligence among relatives, probable etiologies and an empiric recurrence risk. Significant findings include: (1) an increased sex ratio (69% males) of propositi, (2) a significant proportion of patients with clinical manifestations besides MR, (3) virtually no consanguinity among parents, (4) a "positive" family history for over 1/2 of the propositi--about 37% of all children in the sibships were affected; about 21% of the full sibs were affected, (5) a higher number of offspring produced by dull persons and a lower number of offspring from retarded persons compared to two normal persons (6) a proportionately large number of affected children produced from matings involving one or two dull persons, (7) a tendency for dull to have additional dull children and mentally retarded parents to have further retarded children while normal parents with more than one affected child usually had further retarded children, (8) an incidence of affected parents of about 32%, and (9) an overall empiric recurrence risk of 14%. Several etiologies were discussed as possible causes of the condition(s) in this group: (unrecongized) environmental damage and/or maternal/fetal interaction; unrecognized chromosome abnormalities; the homozygous state of several different autosomal recessive gees: X-linked recessive mutations; autosomal dominat new mutations; and mutifactoral inheritance. It was concluded that the group was etiologically heterogeneous and although none of the probable etiologies could be excluded, it seemed reasonable to assume that autosomal recessive inheritance plays an important role in the etiology of severe "pure" mental retardation.