As noted elsewhere,27 such regional effects need not point to differential involvement between brain regions but may simply reflect asynchronous development between them. Consistent with this notion, it is well established that frontal gray matter and the white matter tracts projecting to it show protracted growth.35 Likewise, not all regions are bigger in cases compared with controls. The corpus callosum, the major white matter tract underlying interhemispheric information transfer, for example, is smaller by about 10% in cases compared with controls.36 Separate work showing that frontal and temporal sulci are abnormally shifted in older affected children37 together with evidence of prominent frontal enrichment in the expression of several established ASD genes (B.S.A. and D.H.G., unpublished data, 2009, and findings by Abrahams et al20), however, suggest that these regional findings are most likely the result of differential involvement. These observations also suggest that other genes with such focal frontal or temporal cortical localization in early human brain development may represent candidates of particular interest. Similarly, the protracted patterning of the frontal and temporal cortex may contribute to both the frequency of the ASDs as well as the observed clinical heterogeneity. Although available evidence is limited, regions implicated by imaging and pathological findings generally fit with what is known about the anatomy of social cognition and language, providing a sense of validation between genetics and brain circuits.20,38 Evidence for abnormal development in the second year of life27 together with deficits in structure and function in adults provide a good entry point into neuropathological studies, which we will now discuss.