Long-term course of early onset developmental and epileptic encephalopathy associated with 2q24.3 microduplication

Takuya Masuda; Hitoshi Osaka; Naomi Tsuchida; Satoko Miyatake; Kou Nishimura; Toshiki Takenouchi; Takao Takahashi; Naomichi Matsumoto; Takanori Yamagata

doi:10.1016/j.ebr.2022.100547

Long-term course of early onset developmental and epileptic encephalopathy associated with 2q24.3 microduplication

Epilepsy Behav Rep. 2022 Apr 25:19:100547. doi: 10.1016/j.ebr.2022.100547. eCollection 2022.

Authors

Takuya Masuda¹, Hitoshi Osaka¹, Naomi Tsuchida², Satoko Miyatake², Kou Nishimura³, Toshiki Takenouchi⁴, Takao Takahashi⁴, Naomichi Matsumoto², Takanori Yamagata¹

Affiliations

¹ Department of Pediatrics, Jichi Medical University, 2411-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
² Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
³ Department of Pediatric Neurology, Ise Keiyu Hospital, 2-7-28 Tokiwa, Ise, Mie 516-0041, Japan.
⁴ Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Abstract

Copy number variations (CNVs) have been related to developmental and epileptic encephalopathy (DEE). The 2q24.3 region includes a cluster of genes for voltage-gated sodium channels (SCN) and CNVs in this region cause DEE. However, the long-term course of DEE with a 2q24.3 duplication has not been described. A 20-year-old female developed epileptic encephalopathy in early infancy that was resistant to various antiseizure medications. Her seizures disappeared after starting vitamin B6 therapy. Therefore, her epilepsy was considered pyridoxine-dependent epilepsy. At 16 years old, whole exome sequencing revealed a 2q24.3 microduplication including SCN1A, SCN2A, SCN3A, SCN7A, and SCN9A. Quantitative PCR detected an increased copy number of 1.3 Mb on 2q24.3 involving these genes, but no gene mutation accounting for pyridoxine-dependent epilepsy. Considering that with this duplication she was reported to be seizure-free after infancy, she was able to be off antiseizure medications including vitamin B6. Our case involvingdrug-resistant epilepsy in early infancy had no recurrent seizures during long-term follow up. Detecting CNVs using whole exome sequencing data was useful to identify a 2q24.3 duplication unassociated with pyridoxine-dependent epilepsy, leading to cessation of unnecessary medications.

Keywords: 2q24.3 microduplication; CLB, clobazam; CNVs, copy number variations; CZP, clonazepam; Copy number variations; DEE, developmental and epileptic encephalopathy; Developmental and epileptic encephalopathy; EIEEs, Early infantile epileptic encephalopathies; PB, phenobarbital; PHT, phenytoin; SCN, voltage-gated sodium channels; VPA, valproic acid; Voltage-gated sodium channel; WES, whole exome sequencing; ZNS, zonisamide.

Publication types

Case Reports