A Novel De Novo Variant in KCNH5 in a Patient with Refractory Epileptic Encephalopathy

Akihiko Mitsutake; Takashi Matsukawa; Tatsuhiko Naito; Hiroyuki Ishiura; Jun Mitsui; Hiroaki Harada; Keishi Fujio; Jun Fujishiro; Harushi Mori; Shinichi Morishita; Shoji Tsuji; Tatsushi Toda

doi:10.2169/internalmedicine.3999-24

A Novel De Novo Variant in KCNH5 in a Patient with Refractory Epileptic Encephalopathy

Intern Med. 2024 Aug 1. doi: 10.2169/internalmedicine.3999-24. Online ahead of print.

Authors

Akihiko Mitsutake^{1

2}, Takashi Matsukawa¹, Tatsuhiko Naito¹, Hiroyuki Ishiura^{1

3}, Jun Mitsui^{1

4}, Hiroaki Harada⁵, Keishi Fujio⁵, Jun Fujishiro⁶, Harushi Mori⁷, Shinichi Morishita⁸, Shoji Tsuji^{1

9}, Tatsushi Toda¹

Affiliations

¹ Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
² Department of Neurology, International University of Health and Welfare Mita Hospital, Japan.
³ Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
⁴ Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
⁵ Department of Rheumatology and Allergy, Graduate School of Medicine, The University of Tokyo, Japan.
⁶ Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Japan.
⁷ Department of Radiology, School of Medicine, Jichi Medical University, Japan.
⁸ Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Japan.
⁹ Institute of Medical Genomics, International University of Health and Welfare, Japan.

PMID: 39085070
DOI: 10.2169/internalmedicine.3999-24

Abstract

We herein report a novel de novo KCNH5 variant in a patient with refractory epileptic encephalopathy. The patient exhibited seizures at 1 year and 7 months old, which gradually worsened, leading to a bedridden status. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and cerebellar hypoplasia. A trio whole-exome sequence analysis identified a de novo heterozygous c.640A>C, p.Lys214Gln variant in KCNH5 that was predicted to be deleterious. Recent studies have linked KCNH5 to various epileptic encephalopathies, with many patients showing normal MRI findings. The present case expands the clinical spectrum of the disease, as it is characterized by severe neurological prognosis, cerebral atrophy, and cerebellar hypoplasia.

Keywords: KCNH5; de novo variant; epileptic encephalopathy; whole-exome sequencing.