Atypical genomic cortical patterning in autism with poor early language outcome

Cortical regionalization develops via genomic patterning along anterior-posterior (A-P) and dorsal-ventral (D-V) gradients. Here we find that normative A-P and D-V genomic patterning of cortical surface area (SA) and thickness (CT) present in typically developing and autistic toddlers with good early language outcome, is absent in autistic toddlers with poor early language outcome. Autistic toddlers with poor early language outcome are instead specifically characterized by secondary and independent genomic patterning effect on CT. Genes involved in these effects can be traced back to midgestational A-P and D-V gene expression gradients and different prenatal cell (e.g., progenitor cells, excitatory neurons), are functionally important for vocal learning and human-specific evolution, and are prominent in prenatal co-expression networks enriched for high-penetrance autism risk genes. Autism with poor early language outcome may be explained by atypical genomic cortical patterning starting in prenatal development, which may detrimentally impact later regional functional specialization and circuit formation.