While protein-truncating variants in KCNQ2 tend to cause benign familial epilepsy syndromes of infancy, missense variants may present with a distinct phenotype characterized by neonatal seizures that evolve to drug-resistant DEE and intellectual disability—KCNQ2-related neonatal epileptic encephalopathy (KCNQ2-NEE) (Table 2) [10,45]—although this entity does not always fulfill the clinical criteria for Ohtahara syndrome. Here, KCNQ2 is linked to early-infantile DEE.