MYCN and megalencephaly: While this is in contrast to mTOR pathway mutations, two studies have identified de novo gain-of-function variants in MYCN protogene, a bHLH transcription factor (MYCN) (MIM: 164840) associated with megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly, and neuroblastoma.28