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Review
. 2022 Oct;10(10):e2024.
doi: 10.1002/mgg3.2024. Epub 2022 Jul 30.

Pyridoxine-responsive KCNQ2 epileptic encephalopathy: Additional cases and literature review

Jun Chen  1   2   3 , Qiuji Tao  1   2   3 , Lijuan Fan  1   2   3 , Yajun Shen  1   2   3 , Jinfeng Liu  1   2   3 , Huan Luo  1   2   3 , Zuozhen Yang  4 , Mengmeng Liang  4 , Jing Gan  1   2   3
Affiliations
Review

Pyridoxine-responsive KCNQ2 epileptic encephalopathy: Additional cases and literature review

Jun Chen et al. Mol Genet Genomic Med. 2022 Oct.

Abstract

Background: Typical patients with KCNQ2 (OMIM# 602235) epileptic encephalopathy present early neonatal-onset intractable seizures with a burst suppression EEG pattern and severe developmental delay or regression, and those patients always fail first-line treatment with sodium channel blockers. Vitamin B6, either pyridoxine or pyridoxal 50-phosphate, has been demonstrated to improve seizure control in intractable epilepsy.

Methods: Here, we collected and summarized the clinical data for four independent cases diagnosed with pyridoxine-responsive epileptic encephalopathy, and their exome sequencing data. Moreover, we reviewed all published cases and summarized the clinical features, genetic variants, and treatment of pyridoxine-responsive KCNQ2 epileptic encephalopathy.

Results: All four cases showed refractory seizures during the neonatal period or infancy, accompanied by global development delay. Four pathogenetic variants of KCNQ2 were uncovered and confirmed by Sanger sequencing: KCNQ2 [NM_172107.4: c.2312C > T (p.Thr771Ile), c.873G > C (p.Arg291Ser), c.652 T > A (p.Trp218Arg) and c.913-915del (p. Phe305del)]. Sodium channel blockers and other anti-seizure medications failed to control their seizures. The frequency of seizures gradually decreased after treatment with high-dose pyridoxine. In case 1, case 2, and case 4, clinical seizures relapsed when pyridoxine was withdrawn, and seizures were controlled again when pyridoxine treatment was resumed.

Conclusion: Our study suggests that pyridoxine may be a promising adjunctive treatment option for patients with KCNQ2 epileptic encephalopathy.

Keywords: KCNQ2; epileptic encephalopathy; gene mutation; pyridoxine; pyridoxine-responsive.

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Conflict of interest statement

The authors have no competing interests to declare. Jun Chen and Qiuji Tao contributed equally to this work.

Figures

FIGURE 1
FIGURE 1
KCNQ2 (NM_172107.4) variants detected in our four cases and public database responding to B6. Sanger sequencing confirmed our cases (a). All variants positively responded to B6 (b). #: Case5 was a heterozygous 1.5‐mb deletion (not showed in the figure).
See this image and copyright information in PMC

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References

    1. Allen, N. M. , Mannion, M. , Conroy, J. , Lynch, S. A. , Shahwan, A. , Lynch, B. , & King, M. (2015). The variable phenotypes of KCNQ‐related epilepsy. Epilepsia, 55(9), e99–e105. - PubMed
    1. Clayton, P. T. (2006). B6‐responsive disorders: A model of vitamin dependency. Journal of Inherited Metabolic Disease, 29(2–3), 317–326. - PubMed
    1. Footitt, E. J. , Heales, S. J. , Mills, P. B. , Allen, G. , Oppenheim, M. , & Clayton, P. T. (2011). Pyridoxal 5′‐phosphate in cerebrospinal fluid; factors affecting concentration. Journal of Inherited Metabolic Disease, 34(2), 529–538. - PubMed
    1. Garin Shkolnik, T. , Feuerman, H. , Didkovsky, E. , Kaplan, I. , Bergman, R. , Pavlovsky, L. , & Hodak, E. (2014). Blue‐gray mucocutaneous discoloration: A new adverse effect of ezogabine. JAMA Dermatology, 150(9), 984–989. - PubMed
    1. Goto, A. , Ishii, A. , Shibata, M. , Ihara, Y. , Cooper, E. C. , & Hirose, S. (2019). Characteristics of KCNQ2 variants causing either benign neonatal epilepsy or developmental and epileptic encephalopathy. Epilepsia, 60, 1870–1880. - PMC - PubMed

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