KCNQ2 Encephalopathy and Responsiveness to Pyridoxal-5'-Phosphate

Abstract

KCNQ2 mutations encompass a wide range of phenotypes, ranging from benign familial neonatal seizure to a clinical spectrum of early-onset epileptic encephalopathy that occurs in the early neonatal period. We report an infant with KCNQ2 encephalopathy presenting as neonatal seizure, initially controlled by two anticonvulsants. Electroencephalogram (EEG) showed repetitive multifocal epileptiform discharges, which remained similar after administration of intravenous pyridoxine injection. Seizure recurred at the age of 3 months preceded by an episode of minor viral infection, which occurred multiple times per day. No significant change in seizure frequency was observed after 5-day oral pyridoxine trial, but subsequently, there was dramatic seizure improvement with oral pyridoxal-5'-phosphate (PLP). We hope to alert clinicians that in patients with neonatal epileptic encephalopathy, particularly with known KCNQ2 mutations, intravenous injection of pyridoxine (preferably with EEG monitoring), followed by both oral trial of pyridoxine and PLP should be considered. KCNQ2 mutations should also be considered in vitamin B6-responsive patients.

Keywords: vitamin B 6 -responsive patients; KCNQ2 mutation; epileptic encephalopathy; neonatal seizure; pyridoxal-5′-phosphate; pyridoxine.

Fig. 1

Electroencephalogram before and after pyridoxal-5′-phosphate. ( A ) On the second day of life, it showed a symmetrical background with trace alternant, and repetitive multifocal epileptiform discharges were observed. ( B ) At 4 months of age, after starting on oral pyridoxal-5′-phosphate for 3 weeks. Recorded during sleep. It showed a normal symmetrical background without definitive epileptiform discharges.

Fig. 2

Number of seizures per day since admission, in relation to given medication.

Fig. 3

Electropherogram showing heterozygous missense mutation c.794C > T in exon 5 of KCNQ2 gene in the proband, as compared with a normal control and the parents.