Autism in association with Turner syndrome: Genetic implications for male vulnerability to pervasive developmental disorders

Genetic factors play a substantial part in the aetiology of autism, although no satisfactory model has been proposed that could account for the excess of male phenotypes. We present five cases of autism from an unselected sample of 150 subjects with Turner syndrome, a genetic disorder associated with either the absence, or a structural abnormality, of the second X-chromosome in females. The population prevalence of autism is no more than 1:10,000 normal females. All of the cases considered possessed an intact maternal X-chromosome and a structurally abnormal or absent paternal X-chromosome. We have previously presented evidence that cases of Turner syndrome in which the single X-chromosome is maternal have impaired social cognitive skills, compared with those in whom it is paternal. Based on these earlier findings, we suggested that an imprinted X-linked genetic locus could exist, which is expressed from the paternal X-chromosome of normal females, but which is silent in normal males whose single X is always maternal. This mechanism could serve to protect normal females (who always possess a paternal X-chromosome) from neurodevelopmental disorders affecting social cognition, such as autism. These case reports are the first account of autism in association with Turner syndrome.