De novo RAC1 missense variants have also been identified in NDDs with global developmental delay/intellectual disability and brain size abnormalities as core phenotypes (Mental Retardation autosomal dominant 48, MRD48, OMIM 617751).16 While Rac3 is mainly, if not exclusively, expressed in developing and adult neurons, Rac1 is ubiquitously expressed from the early embryonic stage. This evidence concerns the gene RAC1 and Global developmental delay.