Similar to impairments observed in mouse models of Dravet syndrome and in Scn8aD/+ mice, which express the N1768D SCN8A variant globally, we show here that selective expression of the GOF R1872W variant in PV interneurons is sufficient to induce spontaneous seizures and leads to seizure-induced death (SUDEP) in mice. The gene discussed is SCN8A; the disease is encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy.