J Pediatr Genet 2023; 12(01): 090-094
DOI: 10.1055/s-0040-1721384
Case Report

KCNQ2 Encephalopathy and Responsiveness to Pyridoxal-5′-Phosphate

Chit Kwong Chow
1   Department of Paediatrics and Adolescent Medicine, United Christian Hospital, HKSAR, Hong Kong
Ho Ming Luk
2   Clinical Genetic Service, Department of Health, HKSAR, Hong Kong
Suet Na Wong
3   Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, HKSAR, Hong Kong
› Author Affiliations


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.

Ethical Approval

Written informed consent has been obtained from the family for publication of this case report.

Publication History

Received: 24 August 2020

Accepted: 25 October 2020

Article published online:
07 December 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Nabbout R, Dulac O. Epilepsy. Genetics of early-onset epilepsy with encephalopathy. Nat Rev Neurol 2012; 8 (03) 129-130
  • 2 Kato M, Yamagata T, Kubota M. et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia 2013; 54 (07) 1282-1287
  • 3 Miceli F, Soldovieri MV, Joshi N, Weckhuysen S, Cooper E, Taglialatela M. KCNQ2-related disorders. April 27, 2010 [Updated September 27, 2018]. In: Adam MP, Ardinger HH, Pagon RA. et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020
  • 4 Ohtahara S, Yamatogi Y, Ohtsuka Y. Vitamin B(6) treatment of intractable seizures. Brain Dev 2011; 33 (09) 783-789
  • 5 Saitsu H, Kato M, Koide A. et al. Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome. Ann Neurol 2012; 72 (02) 298-300
  • 6 Milh M, Lacoste C, Cacciagli P. et al. Variable clinical expression in patients with mosaicism for KCNQ2 mutations. Am J Med Genet A 2015; 167A (10) 2314-2318
  • 7 Liu J, Tong L, Song S. et al. Novel and de novo mutations in pediatric refractory epilepsy. Mol Brain 2018; 11 (01) 48
  • 8 Goto A, Ishii A, Shibata M, Ihara Y, Cooper EC, Hirose S. Characteristics of KCNQ2 variants causing either benign neonatal epilepsy or developmental and epileptic encephalopathy. Epilepsia 2019; 60 (09) 1870-1880
  • 9 Na JH, Shin S, Yang D. et al. Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy. Brain Dev 2020; 42 (06) 438-448
  • 10 Biervert C, Schroeder BC, Kubisch C. et al. A potassium channel mutation in neonatal human epilepsy. Science 1998; 279 (5349): 403-406
  • 11 Weckhuysen S, Ivanovic V, Hendrickx R. et al; KCNQ2 Study Group. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology 2013; 81 (19) 1697-1703
  • 12 Geng Y, Hou X. KCNQ2-neonatal epileptic encephalopathy complicated by ventricular tachycardia: a case report. Front Neurol 2020; 11: 263
  • 13 Pisano T, Numis AL, Heavin SB. et al. Early and effective treatment of KCNQ2 encephalopathy. Epilepsia 2015; 56 (05) 685-691
  • 14 Reid ES, Williams H, Stabej PleQ. et al. Seizures due to a KCNQ2 mutation: treatment with vitamin B6. JIMD Rep 2016; 27: 79-84
  • 15 Mefford HC, Cook J, Gospe Jr SM. Epilepsy due to 20q13.33 subtelomere deletion masquerading as pyridoxine-dependent epilepsy. Am J Med Genet A 2012; 158A (12) 3190-3195
  • 16 Klotz KA, Lemke JR, Korinthenberg R, Jacobs J. Vitamin B6-responsive epilepsy due to a novel KCNQ2 mutation. Neuropediatrics 2017; 48 (03) 199-204
  • 17 Weckhuysen S, Mandelstam S, Suls A. et al. KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 2012; 71 (01) 15-25
  • 18 Allen NM, Mannion M, Conroy J. et al. The variable phenotypes of KCNQ-related epilepsy. Epilepsia 2014; 55 (09) e99-e105
  • 19 Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch Dis Child 1999; 81 (05) 431-433
  • 20 Henshall DC, Engel T. P2X purinoceptors as a link between hyperexcitability and neuroinflammation in status epilepticus. Epilepsy Behav 2015; 49: 8-12
  • 21 Thériault O, Poulin H, Thomas GR, Friesen AD, Al-Shaqha WA, Chahine M. Pyridoxal-5′-phosphate (MC-1), a vitamin B6 derivative, inhibits expressed P2X receptors. Can J Physiol Pharmacol 2014; 92 (03) 189-196