Genetics of childhood disorders: XLVI. Autism, part 5: genetics of autism.

Autism is one of the most heritable complex genetic disorders in psychiatry. Despite this high heritability, autism has a heterogeneous etiology, with multiple genes and chromosomal regions likely to be involved. Scientists are using both indirect and direct approaches to identify autism susceptibility genes. Indirect approaches include the characterization of less complex genetic disorders that share some of the symptoms of autism, including Rett syndrome or fragile X syndrome, in the hope that these analyses will provide clues to the more complex disorder of autism (see recent reviews in this space, February and May 2000). Direct approaches include three overlapping methodologies to identify genes or regions of interest in autism: chromosomal methods, such as karyotyping and fluorescence in situ hybridization (FISH); linkage studies, such as genome screens in affected sibling pairs; and gene association studies, including candidate gene studies. These approaches are yielding preliminary findings that are reviewed here. While no specific gene variant has been identified and confirmed that contributes to the expression of autism, it is very likely that several will be confirmed over the next decade. Twin and sibling studies demonstrate heritability in autism. The monozygotic twin of a patient with autism, who shares nearly 100% of nuclear DNA, has an approximately 60% chance of having autism, while the concordance for an autism spectrum disorder is greater than 90%. The dizygotic twin of a patient, who shares 50% of the genes, has approximately the same risk as a sibling, about 4.5%. A member of the general population has approximately 0.2% chance of having autism. Genetics of Childhood Disorders: XLVI. Autism, Part 5: Genetics of Autism