Genetic disorders and the autism spectrum

Objective: Several genetic syndromes are associated with autistic features and are therefore an incentive for the research into the genetic underpinnings of autism spectrum disorders and their putative pathophysiological mechanisms. The most investigated syndromes in this respect are fragile-X syndrome, Rett's disorder, tuberous sclerosis and 22qllmicrodeletion syndrome. In addition, inborn errors of metabolism present with disorders from the autism spectrum whereas a variety of somatic diseases may be accompanied by autistic symptoms that are reversible when adequately treated. Method: Data from own studies in patients with 22q11 microdeletion syndrome are briefly reviewed in combination with those obtained from the literature on other genetic syndromes rather frequently related to autism. Results: Fragile-X syndrome, Rett's disorder, tuberous sclerosis complex, 22qll microdeletion syndrome, and metabolic disorders like X-linked creatine transporter deficiency syndrome, all deal with mutations or copy number variants in genes that code for proteins responsible for neuronal growth and maturation, and/or synaptic functioning Conclusions: From the vast amount of information, it becomes obvious that autism is a very heterogeneous disorder both phenotypically and genotypically, reason why the search for single high impact genes will not be very successful. Focus should be given to the endophenotype strategy to unravel potential gene-brain-behaviour relationships in autism and related disorders.