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Gene mutations in comorbidity of epilepsy and arrhythmia

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Abstract

Epilepsy is one of the most common neurological disorders, and sudden unexpected death in epilepsy (SUDEP) is the most severe outcome of refractory epilepsy. Arrhythmia is one of the heterogeneous factors in the pathophysiological mechanism of SUDEP with a high incidence in patients with refractory epilepsy, increasing the risk of premature death. The gene co-expressed in the brain and heart is supposed to be the genetic basis between epilepsy and arrhythmia, among which the gene encoding ion channel contributes to the prevalence of “cardiocerebral channelopathy” theory. Nevertheless, this theory could only explain the molecular mechanism of comorbid arrhythmia in part of patients with epilepsy (PWE). Therefore, we summarized the mutant genes that can induce comorbidity of epilepsy and arrhythmia and the possible corresponding treatments. These variants involved the genes encoding sodium, potassium, calcium and HCN channels, as well as some non-ion channel coding genes such as CHD4, PKP2, FHF1, GNB5, and mitochondrial genes. The relationship between genotype and clinical phenotype was not simple linear. Indeed, genes co-expressed in the brain and heart could independently induce epilepsy and/or arrhythmia. Mutant genes in brain could affect cardiac rhythm through central or peripheral regulation, while in the heart it could also affect cerebral electrical activity by changing the hemodynamics or internal environment. Analysis of mutations in comorbidity of epilepsy and arrhythmia could refine and expand the theory of “cardiocerebral channelopathy” and provide new insights for risk stratification of premature death and corresponding precision therapy in PWE.

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  1. Cheng Yu and Xue-jun Deng contributed equally. Corresponding author: Da Xu, 498688793@qq.com.

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  1. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China

    Cheng Yu, Xue-jun Deng & Da Xu

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Yu, C., Deng, Xj. & Xu, D. Gene mutations in comorbidity of epilepsy and arrhythmia. J Neurol 270, 1229–1248 (2023). https://doi.org/10.1007/s00415-022-11430-2

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