Autism as a sequence: from heterochronic germinal cell divisions to abnormalities of cell migration and cortical...

The considerable heterogeneity in the number and severity of symptoms observed in autism spectrum disorders (ASD) has been regarded as an obstacle to any future research. Some authors believe that clinical heterogeneity results from the complex interplay of the many genetic and environmental factors that themselves define a condition as multifactorial. However, it is important to note that neuropathological findings in both idiopathic and syndromic autism suggests a single pathophysiological mechanism acting during brain development: the heterochronic division of germinal cells and subsequent migrational abnormalities of daughter cells to their target fields. Multiple exogenous (e.g., viruses, drugs) and endogenous (e.g., genetic mutations) factors are known to disrupt the division of germinal cells and provide for an autism phenotype. The variety of endogenous and exogenous factors, their timing of action during brain development, and the genetic susceptibility of affected individuals (a Triple Hit hypothesis) may all account for the clinical heterogeneity of ASD.