Emerging X-linked genes associated with neurodevelopmental disorders in females

A significant source of risk for neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum disorder (ASD), lies in genes located on the X chromosome. Males can be particularly vulnerable to X-linked variation because of hemizygosity, and male-specific segregation in pedigrees has guided earlier gene discovery for X-linked recessive conditions. More recently, X-linked disorders disproportionally affecting females, with complex inheritance patterns and/or presenting with sex differences, have surfaced. Here, we discuss the genetics and neurobiology of X-linked genes that are paradigmatic to understand NDDs in females. Integrating genetic, clinical, and functional data will be key to understand how X-linked variation contributes to the risk architecture of NDDs.