Recently, we established the megalencephaly-polydactyly syndrome (OMIM #620748) in three individuals harboring heterozygous gain-of-function (GoF) MYCN variants, namely p.(Thr58Met) and p.(Pro60Leu), that helped understanding the MYCN’s roles in human development. The gene discussed is MYCN; the disease is megalencephaly-polydactyly syndrome.