Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 5 2025 A Novel De Novo Variant in KCNH5 in a Patient with Refractory Epileptic Encephalopathy 759 762 EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsuhiko Naito Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroaki Harada Department of Rheumatology and Allergy, Graduate School of Medicine, The University of Tokyo Keishi Fujio Department of Rheumatology and Allergy, Graduate School of Medicine, The University of Tokyo Jun Fujishiro Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University Shinichi Morishita Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo 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. No potential conflict of interest relevant to this article was reported.