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Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6

Research Report

Part of the JIMD Reports book series (JIMD,volume 27)


There is increasing evidence that vitamin B6, given either as pyridoxine or pyridoxal 5′-phosphate, can sometimes result in improved seizure control in idiopathic epilepsy. Whole-exome sequencing was used to identify a de novo mutation (c.629G>A; p.Arg210His) in KCNQ2 in a 7-year-old patient whose neonatal seizures showed a response to pyridoxine and who had a high plasma to CSF pyridoxal 5′-phosphate ratio, usually indicative of an inborn error of vitamin B6 metabolism. This mutation has been described in three other patients with neonatal epileptic encephalopathy. A review of the literature was performed to assess the effectiveness of vitamin B6 treatment in patients with a KCNQ2 channelopathy. Twenty-three patients have been reported to have been trialled with B6; in three of which B6 treatment was used alone or in combination with other antiepileptic drugs to control seizures. The anticonvulsant effect of B6 vitamers may be propagated by multiple mechanisms including direct antagonist action on ion channels, antioxidant action on excess reactive oxygen species generated by increased neuronal firing and replenishing the pool of pyridoxal 5′-phosphate needed for the synthesis of some inhibitory neurotransmitters. Vitamin B6 may be a promising adjunctive treatment for patients with channelopathies and the wider epileptic population. This report also demonstrates that an abnormal plasma to CSF pyridoxal 5′-phosphate ratio may not be exclusive to inborn errors of vitamin B6 metabolism.


  • Anticonvulsant Effect
  • P2X7R Antagonist
  • KCNQ2 Mutation
  • Ohtahara Syndrome
  • Benign Familial Neonatal Seizure

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Competing interests: None declared

Emma S. Reid and Hywel Williams contributed equally to the manuscript.

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We would like to thank the child and her family for participating in this study and for consenting to this report. Additional thanks to Emma Wakeling and Frances Cowen for consenting and referring the patient to our centre, respectively. PBM and PTC are supported by Great Ormond Street Hospital Children’s Charity (GOSHCC). This project was funded by grants from the University College London Impact Award and GOSHCC Metabolic Fund. GOSgene is supported by the NIHR BRC at GOSH for Children NHS Foundation Trust and UCL Institute of Child Health. Views expressed are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

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Correspondence to Peter T. Clayton .

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Communicated by: Nicole Wolf, MD PhD

Take-Home Message

This paper presents a case of KCNQ2 channelopathy showing an apparent response to pyridoxine treatment and indicates that a high plasma to CSF pyridoxal 5′-phosphate ratio is not specific for disorders directly affecting vitamin B6 metabolism.

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Conflict of Interest

Emma S. Reid, Hywel Williams, Polona Le Quesne Stabej, Chela James, Louise Ocaka, Chiara Bacchelli, Emma J. Footitt, Stewart Boyd, Maureen A. Cleary, Philippa B. Mills and Peter T. Clayton declare that they have no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

All authors have read the manuscript and agreed to it being submitted for publication. All individuals listed as authors meet the appropriate authorship criteria, nobody who qualifies for authorship has been omitted from the list, contributors and their funding sources have been properly acknowledged, and all authors and contributors have approved the acknowledgement of their contributions. Emma Reid contributed to data analysis and wrote and submitted the manuscript. Hywel Williams, Polona Le Quesne Stabej, Chela James and Louise Ocaka together prepared the DNA samples for whole-exome sequencing, analysed the data and confirmed the pathogenic mutation. Emma Footitt submitted the initial application for whole-exome sequencing to be carried out. Chiara Bacchelli considered and accepted the application for sequencing. Peter Clayton, Maureen Cleary, Emma Footitt and Emma Reid consulted with the patient and her family regarding the research and the results of the study. Stewart Boyd reviewed all EEGs from the patient. Philippa Mills and Peter Clayton made large contributions to the critical revision of the manuscript. All authors had access to the study data that support this publication.

Electronic Supplementary Material

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Data S1: Clinical details of the 23 patients identified who have mutations in KCNQ2 that have been trialled on treatment with pyridoxine or pyridoxal 5′-phosphate. Responses to treatment are stated where available

Data S2: Plasma amino acid analysis


Data S3: Whole-exome sequencing and touchdown polymerase chain reaction (PCR) conditions

Data S4: Plasma PLP reference ranges

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Reid, E.S. et al. (2015). Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6 . In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 27. JIMD Reports, vol 27. Springer, Berlin, Heidelberg.

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