The association between autism and errors in early embryogenesis: what is the causal mechanism?

The association between embryonic errors and the development of autism has been recognized in the literature, but the mechanism underlying this association remains unknown. We propose that pleiotropic effects during a very early and specific stage of embryonic development-early organogenesis-can explain this association. In humans early organogenesis is an embryonic stage, spanning Day 20 to Day 40 after fertilization, which is characterized by intense interactivity among body parts of the embryo. This implies that a single mutation or environmental disturbance affecting development at this stage can have several phenotypic effects (i.e., pleiotropic effects). Disturbances during early organogenesis can lead to many different anomalies, including limb deformities, craniofacial malformations, brain pathology, and anomalies in other organs. We reviewed the literature and found ample evidence for the association between autism and different kinds of physical anomalies, which agrees with the hypothesis that pleiotropic effects are involved in the development of autism. The proposed mechanism integrates findings from a variety of studies on autism, including neurobiological studies and studies on physical anomalies and prenatal influences on neurodevelopmental outcomes. The implication is that the origin of autism can be much earlier in embryologic development than has been frequently reported. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.