KCNQ2 pathogenic variants in early-infantile developmental and epileptic encephalopathy in Indonesia
DOI:
https://doi.org/10.31117/neuroscirn.v8i2.364Keywords:
KCNQ2, Whole-exome sequencing, Single gene test, Indonesia, Early infantile developmental, Epileptic encephalopathiesAbstract
Early-infantile developmental and epileptic encephalopathies (EIDEE) are characterized by developmental delays and life-threatening seizures beginning in the early infantile period. The most frequent genetic cause of neonatal epilepsy is KCNQ2-associated genetic epilepsy. We determined the pathogenic variant in EIDEE cases using KCNQ2 variant screening and whole-exome sequencing (WES) approaches. The subjects were children <18 years of age with EIDEE in our hospital. We performed the KCNQ2 pathogenic variant screening using PCR on four exons and WES in our patients. We involved six patients: three males and three females, with the patient age range between 2 and 15 months old at the time of blood sampling. One pathogenic variant in exon 6 of the KCNQ2 gene, c.868G>A (p.Gly290Ser), was found in one patient. In addition, two synonymous SNVs were also found in our patient. Our study identifies one pathogenic variant in the KCNQ2 gene in one EIDEE patient. These findings led us to give the patient a sodium channel blocker, which led to improved outcomes. Our study also suggests the importance of the KCNQ2 pathogenic variant screening for selected EIDEE patients.
References
Berg, A. T., Mahida, S., & Poduri, A. (2021). KCNQ2 ‐DEE: Developmental or epileptic encephalopathy? Annals of Clinical and Translational Neurology, 8(3), 666–676. https://doi.org/10.1002/acn3.51316
Fang, Z., Zhang, M., Xie, L., Jiang, L., Hong, S., Li, X., Hu, Y., & Chen, J. (2019). KCNQ2 related early-onset epileptic encephalopathies in Chinese children. Journal of Neurology, 266(9), 2224–2232. https://doi.org/10.1007/s00415-019-09404-y
Kato, M., Yamagata, T., Kubota, M., Arai, H., Yamashita, S., Nakagawa, T., FujII, T., Sugai, K., Imai, K., Uster, T., Chitayat, D., Weiss, S., Kashii, H., Kusano, R., Matsumoto, A., Nakamura, K., Oyazato, Y., Maeno, M., Nishiyama, K., Kodera, H., Nakashima, M., Tsurusaki, Y., Miyake, N., Saito, K., Hayasaka, K., Matsumoto, N., & Saitsu, H. (2013). Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia, 54(7), 1282–1287. https://doi.org/10.1111/epi.12200
Kuersten, M., Tacke, M., Gerstl, L., Hoelz, H., Stülpnagel, C. v., & Borggraefe, I. (2020). Antiepileptic therapy approaches in KCNQ2 related epilepsy: A systematic review. European Journal of Medical Genetics, 63(1), 103628. https://doi.org/10.1016/j.ejmg.2019.02.001
Lee, I., Chang, T., Liang, J., & Li, S. (2019). KCNQ2 mutations in childhood nonlesional epilepsy: Variable phenotypes and a novel mutation in a case series. Molecular Genetics & Genomic Medicine, 7(7), e00816. https://doi.org/10.1002/mgg3.816
Lee, I. C., Chang, M. Y., Liang, J. S., & Chang, T. M. (2021). Ictal and interictal electroencephalographic findings can contribute to early diagnosis and prompt treatment in KCNQ2-associated epileptic encephalopathy. Journal of the Formosan Medical Association, 120(1), 744–754. https://doi.org/10.1016/j.jfma.2020.08.014
Lee, I. C., Yang, J. J., Liang, J. S., Chang, T. M., & Li, S. Y. (2017). KCNQ2-associated neonatal epilepsy: phenotype might correlate with genotype. Journal of Child Neurology, 32(8), 704–711. https://doi.org/10.1177/0883073817701873
National Center for Biotechnology Information. (n.d.-a). ClinVar; [VCV000129345.19] [Dataset]. Retrieved December 2, 2022, from https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000129345.19
National Center for Biotechnology Information. (n.d.-b). ClinVar; [VCV000138016.11] [Dataset]. Retrieved December 2, 2022, from https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000138016.11
Olson, H. E., Kelly, M., LaCoursiere, C. M., Pinsky, R., Tambunan, D., Shain, C., Ramgopal, S., Takeoka, M., Libenson, M. H., Julich, K., Loddenkemper, T., Marsh, E. D., Segal, D., Koh, S., Salman, M. S., Paciorkowski, A. R., Yang, E., Bergin, A. M., Sheidley, B. R., & Poduri, A. (2017). Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression. Annals of Neurology, 81(3), 419–429. https://doi.org/10.1002/ana.24883
Pisano, T., Numis, A. L., Heavin, S. B., Weckhuysen, S., Angriman, M., Suls, A., Podesta, B., Thibert, R. L., Shapiro, K. A., Guerrini, R., Scheffer, I. E., Marini, C., & Cilio, M. R. (2015). Early and effective treatment of KCNQ 2 encephalopathy. Epilepsia, 56(5), 685–691. https://doi.org/10.1111/epi.12984
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., & Rehm, H. L. (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405–424. https://doi.org/10.1038/gim.2015.30
Seo, G. H., Kim, T., Choi, I. H., Park, J., Lee, J., Kim, S., Won, D., Oh, A., Lee, Y., Choi, J., Lee, H., Kang, H. G., Cho, H. Y., Cho, M. H., Kim, Y. J., Yoon, Y. H., Eun, B., Desnick, R. J., Keum, C., & Lee, B. H. (2020). Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE. Clinical Genetics, 98(6), 562–570. https://doi.org/10.1111/cge.13848
Zeng, Z., & Bromberg, Y. (2019). Predicting functional effects of synonymous variants: A systematic review and perspectives. Frontiers in Genetics, 10, 914. https://doi.org/10.3389/fgene.2019.00914
Zuberi, S. M., Wirrell, E., Yozawitz, E., Wilmshurst, J. M., Specchio, N., Riney, K., Pressler, R., Auvin, S., Samia, P., Hirsch, E., Galicchio, S., Triki, C., Snead, O. C., Wiebe, S., Cross, J. H., Tinuper, P., Scheffer, I. E., Perucca, E., Moshé, S. L., & Nabbout, R. (2022). ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia, 63(6), 1349–1397. https://doi.org/10.1111/epi.17239
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Copyright (c) 2025 Agung Triono, Elisabeth Siti Herini, Kristy Iskandar, Marissa Leviani Hadiyanto, Kania Diantika, Veronica Wulan Wijayanti, Gunadi
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