Chapter 2.1 - Etiological Heterogeneity in Autism Spectrum Disorders: Role of Rare Variants

Abstract

Autism spectrum disorders (ASD) encompass a group of behaviorally defined developmental disabilities characterized by marked clinical and etiological heterogeneity. There is increasing evidence that ASD can arise from rare highly penetrant mutations and genomic imbalances. There are at present over 100 disease genes and 50 recurrent genomic imbalances implicated in the etiology of ASD. These genes and loci have so far all been causally implicated in intellectual disability, indicating that these two neurodevelopmental disorders share common genetic bases. Similarly, many genes involved in epilepsy can also result in ASD. These observations indicate that these genes cause a continuum of neurodevelopmental disorders that manifest in different ways depending on other genetic, environmental or stochastic factors. Increased recognition of the etiological heterogeneity of ASD will expand the number of target genes for neurobiological investigations, reveal functional pathways and assist the development of novel therapeutic approaches.