Clinical Feature, Treatment, and KCNH5 Mutations in Epilepsy

Xiufu Hu; Junli Yang; Man Zhang; Tie Fang; Qin Gao; Xinjie Liu

doi:10.3389/fped.2022.858008

Clinical Feature, Treatment, and KCNH5 Mutations in Epilepsy

Front Pediatr. 2022 Jul 7:10:858008. doi: 10.3389/fped.2022.858008. eCollection 2022.

Authors

Xiufu Hu¹, Junli Yang¹, Man Zhang², Tie Fang³, Qin Gao⁴, Xinjie Liu¹

Affiliations

¹ Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.
² The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Beijing Children's Hospital, Beijing, China.
⁴ Beijing MyGenostics Co., Ltd, Beijing, China.

Abstract

The voltage-gated Kv10.2 potassium channel, encoded by KCNH5, is broadly expressed in mammalian tissues, including the brain. Its potential mechanism remains unclear. According to previous studies, dysfunction of Kv10.2 may be associated with epileptic encephalopathies and autism spectrum disorder (ASD). To date, only one disease-causing mutation of KCNH5 has been reported, and it involves a case that presented with seizures and autism symptoms. In this study, we discovered and characterized three de novo mutations in KCNH5 that potentially caused severe conditions observed in three Chinese children. All of them experienced seizures, two of them presented with epileptic encephalopathy, one of them presented with ASD, and one did not relapse after drug withdrawal. Notably, treatment with antiepileptic drugs (AEDs) was effective in all patients whose epileptic seizures were controlled. The structures of the proteins resulting from the mutations were predicted in two of the three cases. This provides powerful insight into clinical heterogeneity and genotype-phenotype correlation in KCNH5-related diseases.

Keywords: KCNH5; clinical manifestations; epilepsy; molecular characterization; treatment.