Though successful in Mecp2 mutant mice that model Rett syndrome (Tropea et al., 2009; Castro et al., 2014), intervening on the GH-IGF1 axis was not able to reverse neuropsychiatric defects associated with Arid1b. Our findings not only functionally validate ARID1B’s involvement in human disease, they suggest underappreciated clinical manifestations of human ARID1B mutations that can be approached from a treatment-perspective. Here, ARID1B is linked to atypical Rett syndrome.