STXBP1 plays a non-redundant role in neurotransmission: genetic deletion of STXBP1 results in embryonic lethality in mice (19), and de novo mono-allelic mutations in humans invariably result in epileptic encephalopathy (a rare form of Dravet syndrome) (20). Here, STXBP1 is linked to encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy.