Early behavioral indices of inherited liability to autism.

OBJECTIVE

The observed heterogeneity of autism spectrum disorder (ASD)-and the diversity of rare germline mutations with which it has been associated-has been difficult to reconcile with knowledge of its pronounced heritability in the population.

METHODS

This article reviews and synthesizes recent family and developmental studies incorporating behavioral indices of inherited risk for ASD.

RESULTS

Autism may arise from critical combinations of early inherited neurobehavioral susceptibilities-some specific to autism, some not-each of which may be traceable to partially-independent sets of genetic variation. These susceptibilities and their respective genetic origins may not relate to the characterizing symptoms of autism (after it develops) in a straightforward way, and may account for "missing heritability" in molecular genetic studies.

CONCLUSIONS

Within-individual aggregations of a finite set of early inherited neurobehavioral susceptibilities-each individually common in the population-may account for a significant share of the heritability of ASD. Comprehensive identification of these underlying traits my help elucidate specific early intervention targets in individual patients, especially if autism represents a developmental consequence of earlier-interacting susceptibilities. Scientific understanding of the early ontogeny of autism will benefit from epidemiologically-rigorous, genetically-informative studies of robust endophenotypic candidates whose inter-relationships in infancy are mapped and normed.