Although these complex neurodevelopmental disorders remain a primary interest of the current review, important insights to address this issue were gained from the studies focusing on the APA-linked Mendelian disorders (for example, achondroplasia, Apert and Costello syndromes) and their causal mutations in the FGFR2, FGFR3, PTPN11, HRAS and RET genes. Here, HRAS is linked to Costello syndrome.