Autism spectrum disorders (ASDs) are a complex group of neurodevelopmental disorders typically identified in childhood. ASDs are characterized by social interaction deficits, communication impairments, and repetitive behaviors. Due to the heterogeneous nature of ASDs, defining the specific phenotype and the underlying etiology has been difficult. Recent literature reports have identified sequence variants in the phosphatase and tensin homolog (PTEN) gene in children with ASD and enlarged head size (macrocephaly), particularly in families with a known PTEN-related syndrome. PTEN is a tumor suppressor gene implicated in Cowden syndrome (CS), Bannayan- Riley-Ruvalcaba syndrome (BRRS), and Proteus and Proteus-like syndromes. Since considerable phenotypic overlap exists among these allelic conditions, the term PTEN hamartoma tumor syndrome (PHTS) has been adopted to describe the group of conditions as a whole. Due to the association of PTEN with overgrowth and neurobehavioral manifestations, recent research has
focused on autism/ASD and macrocephaly related to PTEN sequence variants.