Autisms

Autism is a complex behavioral disorder with onset during early childhood and typically a life-long course. It is characterized by deficits in communication and social interaction, as well as by stereotypic behaviors and restricted patterns of interest. Its incidence has dramatically risen during the last two decades from 2-5/10,000 to approximately 1-2/1,000 children. The most consistently recognized neurobiological underpinning consists in a relative disconnection between distant brain regions, contrasting with local hyperconnectivity. Autism is increasingly recognized as a heterogeneous mixture of developmental disorders with strong genetic underpinnings. We thus hereby provide a genetically-based classification of the “autisms” distinguishing (a) “classical” syndromic forms, due to known cytogenetic aberrations, copy number variants or mitochondrial DNA abnormalities; (b) recently discovered monogenic autisms, due to highly penetrant mutations affecting synaptic, chromatin architecture, morphogenetic, or calcium-related genes; (c) the most widespread forms of polygenic autisms with “multiple-hit” contributions by common genetic variants as well as by gene-environment interactions; and finally (d) teratogenetic forms, due to environmental exposure to drugs, pollutants or viruses. The recognition of the existence of many different “autisms” is not only rich of heuristic potential for future translational research, but is already starting to influence diagnostic and therapeutic strategies at the present time.