Therefore, while targeted single-gene Sanger sequencing may remain appropriate in some cases, for example, typical SCN1A-related phenotypes, EIMFS (KCNT1), classical Rett syndrome (MECP2) and some cases with other dysmorphic syndromes, our data argue for the use of panel-based analysis as the diagnostic genetic test of choice in the majority of individuals with early-onset seizure and severe developmental delay disorders. Here, KCNT1 is linked to atypical Rett syndrome.