L’autisme et les troubles envahissants du développement forment un groupe de pathologies d’origine neurodéveloppementale dont la prévalence semble en constante augmentation. L’implication de facteurs génétiques dans le déterminisme de ces troubles est maintenant largement admise. Cependant, l’identification de ces facteurs et surtout leur mise en correspondances avec des phénotypes définis restent à établir. La complexité phénotypique, ainsi que la probable hétérogénéité de la composante génétique rendent particulièrement complexe la recherche de correspondances génotype/phénotype dans un trouble neurodéveloppemental dont par ailleurs la physiopathologie précise n’est pas connue. Les stratégies d’identifications des facteurs génétiques, des marqueurs phénotypiques, puis de leur mise en correspondance doivent ainsi tenir compte de la modélisation de la composante génétique et des particularités phénotypiques d’un trouble survenant à une période où les processus de développement et de maturation cérébrale sont particulièrement actifs.

Autism spectrum disorders are a class of conditions categorized by communication problems, ritualistic behaviors, and deficits in social behaviors. This class of disorders merges a heterogeneous group of neurodevelopmental disorders regarding some phenotypic and probably physiopathological aspects. Genetic basis is well admitted, however, considering phenotypic and genotypic heterogeneity, correspondences between genotype and phenotype have yet to be established.

To better identify such correspondences, genetic models have to be identified and phenotypic markers have to be characterized. Recent insights show that a variety of genetic mechanisms may be involved in autism spectrum disorders, i.e. single gene disorders, copy number variations and polygenic mechanisms. These current genetic models are described. Regarding clinical aspects, several approaches can be used in genetic studies. Nosographical approach, especially with the concept of autism spectrum disorders, merges a large group of disorders with clinical heterogeneity and may fail to identify clear genotype/phenotype correlations. Dimensional approach referred in genetic studies to the notion of “Broad Autism Phenotype” related to a constellation of language, personality, and social-behavioral features present in relatives that mirror the symptom domains of autism, but are much milder in expression. Studies of this broad autism phenotype may provide a potentially important complementary approach for detecting the genes involved in these domains. However, control population used in those studies need to be well characterized too. Identification of endophenotypes seems to offer more promising results. Endophenotypes, which are supposed to be more proximal markers of gene action in the same biological pathway, linking genes and complex clinical symptoms, are thought to be less genetically complex than the broader disease phenotype, indexing a limited aspect of genetic risk for the disorder as a whole. However, strategies useful to characterize such phenotypic markers (for example, electrophysiological markers) have to take into account that autism is an early neurodevelopmental disorder occurring during childhood when brain development and maturation are in process.

Recent genetic results have improved our knowledge in genetic basis in autism. Nevertheless, correspondences with phenotypic markers remain challenging according to phenotypic and genotypic heterogeneity.