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KCNQ2 related early-onset epileptic encephalopathies in Chinese children

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Abstract

Objective

To study the phenotype, genotype, treatment strategies, and short-term prognosis of Chinese children with KCNQ2 (potassium voltage-gated channel subfamily Q member 2) related early-onset epileptic encephalopathies (KCNQ2-EOEEs) in Southwest China.

Methods

We used targeted next-generation sequencing (NGS) to identify KCNQ2 variants in Chinese patients with EOEEs. And patients with KCNQ2-EOEEs were confirmed after clinical and genetic analyses. We followed them in our cohort and analyzed their clinical data.

Results

122 patients with EOEEs were registered from August 2015 to October 2017, and 78 underwent targeted NGS. Seven among them were confirmed to be caused by pathogenic KCNQ2 variants, 6 of that were de novo and 1 was inherited. The median seizure onset age of the 7 patients was 5 days. Tonic–clonic and tonic seizures were the major seizure types; the electroencephalograms of all patients showed multifocal sharp waves initially. When new seizure types appeared in infancy, the most common type was epileptic spasm. At the last follow-up, seizures persisted in only one patient, and another patient had seizure recurrence. The identified pathogenic KCNQ2 variants introduced amino acid missense changes, or in one instance, frameshift variant, four of which have not been reported. Valproic acid (VPA) was effective as concomitant treatment in three patients, and all patients had intellectual/developmental disabilities (IDDs).

Conclusions

The KCNQ2 missense variant plays an important role in EOEE pathogenesis, and patients with KCNQ2-EOEEs mainly present with intractable seizures and IDDs. Moreover, VPA has potential as an effective therapeutic strategy.

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Acknowledgements

This work was supported by the Omics-based Precision Medicine of Epilepsy being entrusted by Key Research Project of the Ministry of Science and Technology of China (Grant 2016YFC0904400) and The Clinical Research Program of Children’s Hospital of Chongqing Medical University(Grant [2015]45-1cyj2015-7). The funding body had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. Zhi-xu Fang and Min Zhang contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Neurology, Children’s Hospital of Chongqing Medical University, No. 136, Zhongshan Er Road, Yuzhong District, Chongqing, 400014, China

    Zhi-xu Fang, Ling-ling Xie, Li Jiang, Si-qi Hong, Xiu-juan Li, Yue Hu & Jin Chen

  2. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China

    Zhi-xu Fang, Min Zhang, Ling-ling Xie, Li Jiang, Si-qi Hong, Xiu-juan Li, Yue Hu & Jin Chen

  3. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China

    Zhi-xu Fang, Min Zhang, Ling-ling Xie, Li Jiang, Si-qi Hong, Xiu-juan Li, Yue Hu & Jin Chen

  4. Chongqing Key Laboratory of Pediatrics, Chongqing, China

    Zhi-xu Fang, Min Zhang, Ling-ling Xie, Li Jiang, Si-qi Hong, Xiu-juan Li, Yue Hu & Jin Chen

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  1. Zhi-xu Fang
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Correspondence to Ling-ling Xie.

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This study was approved by the Children’s Hospital of Chongqing Medical University Ethics Committee.

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Fang, Zx., Zhang, M., Xie, Ll. et al. KCNQ2 related early-onset epileptic encephalopathies in Chinese children. J Neurol 266, 2224–2232 (2019). https://doi.org/10.1007/s00415-019-09404-y

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  • DOI: https://doi.org/10.1007/s00415-019-09404-y

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