Aetiology of ASD: can genetic studies help?

Abstract

Autism is a debilitating neuro-developmental disorder that is typically apparent by age 3 years. It is characterized by impaired communication, impaired reciprocal social interaction skills, and by restricted repetitive behaviors and interests. Autism spectrum disorder (ASD) is a broader phenotype which includes autism as well as less severe conditions such as Asperger syndrome and Pervasive Developmental disorder- not otherwise specified (PDD-NOS). The most recent estimate of the prevalence of autism is 3 per 1000 and rises to 6 per 1000 when all forms of ASDs are included. It occurs 4 times more commonly in males than in females.

The ASDs are etiologically heterogeneous. About 10% are associated with a Mendelian syndrome e.g. Fragile X syndrome and tuberous sclerosis complex. Another 5-7% are associated with a cytogenetically visible chromosome abnormality. Until a few years ago, the remaining is presumed to be multi-factorial and linkage scans have mapped potential candidate risk loci. More recently, array CGH studies have shown that de novo copy number variations (CNVs) occur in 7-10% of idiopathic ASD patients and that some of them have a syndromic appearance. Genes affected by CNVs are good candidates for research into ASD susceptibility. However, the complexity of autism genetics mandates that the biomedical relevance of these CNVs and the affected genes be approached in an integrated context.