Heritable and nonheritable risk factors for autism spectrum disorders.

Autism spectrum disorders (ASDs) are developmental disabilities where language development is absent or delayed, rote or repetitive behaviors typically emerge, and nonverbal communication, imagination, and social interactions are profoundly hindered (1). The severity of impairment in each of these dimensions can be quite variable, as can individual cognitive functioning (2). However, even higher-functioning persons with ASD are confronted with significant lifelong challenges. The first clinical descriptions of ASD were offered almost simultaneously by psychiatrist Leo Kanner and pediatrician Hans Asperger in the early 1940s. In his original paper, Kanner remarked on “the children’s aloneness from the beginning of life” (3, p. 250), implying that the constellation of behaviors that he observed was the result of pathology he believed to be present at birth. Despite this, because few autistic offspring had autistic parents, no obvious chromosomal anomalies were consistently found among autistic children, and the sibling recurrence rate was erroneously thought to be low (first estimated at only around 2 percent), geneticists initially doubted a role for heredity in ASD etiology (4). It was the publication of the first twin study on autistic disorder (5) that stimulated a stark change in the conventional wisdom. Findings of substantive differences in monozygotic-dizygotic twin concordance in the original and subsequent twin studies, coupled with higher estimates of sibling recurrence from studies conducted in the 1980s, indicated strongly that liability to ASD was heritable. Unfortunately, the subsequent two decades of genetic studies have failed to reveal a satisfactorily complete picture of ASD etiology. This paper provides a review of ASD epidemiology, focusing first on what is known about heritable and nonheritable risk factors and concluding with a discussion of a more novel epidemiologic study design that blends elements of family-based and association studies in a way that may be necessary to explicate the risk factors underlying this major neurodevelopmental disorder.