Five variants across four epilepsy-related genes (DEPDC5, CHD2, SCN8A and IQSEC2), all VUS by ACMG-AMP criteria alone, were considered to offer an independent molecular diagnosis, alongside the known SCN1A variant, resulting in blended phenotypes including features of both Dravet syndrome and the additional epilepsy-related genetic disorder. This evidence concerns the gene DEPDC5 and encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy.