Previously reported mutations in Akt1, Akt2, and Akt3 associated with Proteus Syndrome, several cancers, and megalencephalies (33, , , , –38) and mutations in Akt1 that drive growth factor-independent cell survival in vitro (39) all map to the autoinhibitory interface (Fig. 1D). This evidence concerns the gene AKT1 and megalencephaly.