Teratogenic Alleles in Autism and Other Neurodevelopmental Disorders

Abstract

Genes for neurodevelopmental disorders have proven difficult to find. In the case of autism, even though a number of genes associated with the disorder have been identified, the cause of the disorder is far from clear. We discuss here a new category of genetic contribution to human disorders, i.e., gene variants (alleles) that act in mothers during pregnancy to contribute to the neurodevelopmental disorder in her offspring. We have termed these maternally acting alleles "teratogenic alleles" because they act in the fetus in a way somewhat analogous to chemical teratogens or drug teratogens ingested by a mother during pregnancy that act to damage her fetus. Although two examples of this mechanism have been known for some time, new examples have been found and since 2003 the number of examples has more than doubled. Even though this number is growing rapidly, the present number, 33, is not large. It is not clear whether this is so because teratogenic alleles are not yet well known and therefore not looked for, whether the possibility of a teratogenic allele is not considered when studies are designed, or whether there are in fact very few teratogenic alleles in comparison with alleles that act in the fetus. All of the teratogenic alleles reported so far have been in neurodevelopmental and developmental disorders. Again it is not clear whether this is simply because these are the disorders that happen to have been studied so far by suitable study designs, or whether teratogenic alleles are actually more commonly encountered in these disorders, perhaps as a regular feature or even as a characteristic feature of these disorders. In autism, some of the brain abnormalities are known to occur very early in pregnancy. A number of teratogenic alleles have already been reported in autism and more will be reported. Demonstration of the action of teratogenic alleles in autism opens up new opportunities for therapy and prevention. (PsycInfo Database Record (c) 2020 APA, all rights reserved)