The present results provide the first clinical, genetic, and functional evidence for a severe phenotype associated with a homozygous loss‐of‐function (LoF) variant in KCNQ3 and highlight previously unrecognized difference in genetic and pathogenetic mechanisms between KCNQ2‐ and KCNQ3‐related epilepsies. This evidence concerns the gene KCNQ3 and epilepsy.