Benign Familial Neonatal Seizures (BFNS) is a rare, autosomal-dominant epilepsy of the newborn caused by mutations in K v7.2 (KCNQ2) or K v7.3 (KCNQ3) genes encoding for neuronal potassium (K +) channel subunits. In this study, we describe a sporadic case of BFNS; the affected child carried heterozygous missense mutations in both K v7.2 (D212G) and K v7.3 (P574S) alleles. Electrophysiological experiments revealed that the K v7.2 D212G substitution, neutralizing a unique negatively-charged residue in the voltage sensor of K v7.2 subunits, altered channel gating, leading to a marked destabilization of the open state, a result consistent with structural analysis of the K v7.2 subunit, suggesting a possible pathogenetic role for BFNS of this K v7.2 mutation. By contrast, no significant functional changes appeared to be prompted by the K v7.3 P574S substitution. Computational modelling experiments in CA1 pyramidal cells revealed that the gating changes introduced by the K v7.2 D212G increased cell firing frequency, thereby triggering the neuronal hyperexcitability which underlies the observed neonatal epileptic condition.