In 34 adults with SCN1A-related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. This evidence concerns the gene DEPDC5 and encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy.