Three strongly activating PIK3CA mutations found most commonly in cancer (hotspot mutations) result in severe segmental cortical dysplasia (SEGCD), which includes bilateral dysplastic megalencephaly (MEG), hemimegalencephaly (HMEG) and focal cortical dysplasia (FCD) types 2a/2b (Lee et al., 2012; D'Gama et al., 2015; Conway et al., 2007; Jansen et al., 2015). This evidence concerns the gene PIK3CA and megalencephaly.