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

Epilepsy & Behavior Reports (Jan 2022)

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

Affiliations

Takuya Masuda: Department of Pediatrics, Jichi Medical University, 2411-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
Hitoshi Osaka: Department of Pediatrics, Jichi Medical University, 2411-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan; Corresponding author at: Division of Pediatrics, Jichi Medical University, 2411-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Naomi Tsuchida: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Satoko Miyatake: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Kou Nishimura: Department of Pediatric Neurology, Ise Keiyu Hospital, 2-7-28 Tokiwa, Ise, Mie 516-0041, Japan
Toshiki Takenouchi: Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Takao Takahashi: Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Naomichi Matsumoto: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Takanori Yamagata: Department of Pediatrics, Jichi Medical University, 2411-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan

Journal volume & issue: Vol. 19
p. 100547

Abstract

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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.

Published in Epilepsy & Behavior Reports

ISSN: 2589-9864 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system; Science: Physiology: Neurophysiology and neuropsychology
Website: https://www.journals.elsevier.com/epilepsy-and-behavior-reports

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