Furthermore, we show that a subset of patients with the catastrophic early-onset Dravet syndrome who commonly have mutations in SCN1A also harbor mutations in SCN9A. This finding is important as it demonstrates for the first time mutational evidence for a modifying digenic mechanism of human epilepsy. This evidence concerns the gene SCN1A and encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy.