Monozygotic twins with tuberous sclerosis discordant for the severity of developmental deficits

Abstract

A pair of monozygotic male twins with tuberous sclerosis (TS) were followed between 18 months and 3 years of age. Twin A with 25 large cortical tubers and hence extensive brain involvement was moderately mentally retarded and met criteria for autism. The other twin had more (n = 31) but smaller tubers. He was not mentally retarded and did not meet criteria for autism. This study provides evidence that nongenetic factors such as extent of brain abnormality and not just number of cortical tubers are important in determining phenotypic variability in TS. The findings also raise questions about the mechanisms giving rise to autism in TS.