Autism and mental retardation (MR) represent an etiologic enigma for clinicians and scientists. It is however considered that these conditions are closely related and are also associated with genetic alterations. The aim of this presentation is to provide an update of findings indicating that MR and autism share some common genetic causes, and to address questions of the cognitive functions involved in these brain disorders.

Various genetic strategies have shown that autism and MR are associated with identical mutations, raising the hypothesis of common genetic causes. Particularly, the characterization of chromosomal abnormalities has led to define some genomic territories encompassing candidate genes. Furthermore, the study of individuals or families with X-linked MR indicated a significant number of patients with both MR and autism.

Interestingly, many genes involved in autism and MR disorders encode proteins of the postsynaptic density proteome network. Mouse genomic studies have shown specific cognitive abnormalities indicating that the postsynaptic proteome seems to be crucial for the establishment and/or maintenance of the normal cognitive function.

A close relationship exists between MR and autism since 75% of people with autism suffer from MR of varying degree, and 20-30% of people with severe MR exhibit some autistic features. Accumulating data also provides evidence that similar neurobiological pathways would affect both MR and autism. The study of syndromic forms of autism associated with MR should provide a powerful basis for the identification and the understanding of the pathophysiological pathways underlying these two conditions.