SHANK3 and Down syndrome: Significant advancements in identifying molecular mechanisms involved in ASD have been made by studying common ASD comorbidities with Mendelian inheritance patterns such as Tuberous Sclerosis (TSC1/2), Rett syndrome (MECP2), Fragile X syndrome (FMR1), Phellan-McDermid (SHANK3), Angelman (UBE3A), and Cowden (PTEN) syndromes, but altogether these disorders do not account for more than 10% of ASD cases (Sztainberg and Zoghbi, 2016).