title: Quinidine therapy for West syndrome with KCNTI mutation: A case report.
abstract: The KCNT1 gene encodes the sodium-dependent potassium channel, with quinidine being a partial antagonist of the KCNT1 channel. Gain-of-function KCNT1 mutations cause early onset epileptic encephalopathies including migrating partial seizures of infancy (MPSI). At 5months of age, our patient presented with epileptic spasms and hypsarrhythmia by electroencephalogram. Psychomotor retardation was observed from early infancy. The patient was diagnosed with West syndrome. Consequently, various anti-epileptic drugs, adrenocorticotropic hormone therapy (twice), and ketogenic diet therapy were tried. However, the epileptic spasms were intractable. Whole exome sequencing identified a KCNT1 mutation (c.1955G>T; p.G652V). At 2years and 6months, the patient had daily epileptic spasms despite valproate and lamotrigine treatment, and was therefore admitted for quinidine therapy. With quinidine therapy, decreased epileptic spasms and decreased epileptiform paroxysmal activity were observed by interictal EEG. Regarding development, babbling, responsiveness, oral feeding and muscle tone were ameliorated. Only transient diarrhea was observed as an adverse effect. Thus, quinidine therapy should be attempted in patients with West syndrome caused by KCNT1 mutations, as reported for MPSI.
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
authors: Masataka
authors: M
authors: Fukuoka
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan. Electronic address: i-kuki@med.osakacity-hp.or.jp.
authors: Ichiro
authors: I
authors: Kuki
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
authors: Hisashi
authors: H
authors: Kawawaki
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
authors: Shin
authors: S
authors: Okazaki
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
authors: Kiyohiro
authors: K
authors: Kim
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
authors: Yuka
authors: Y
authors: Hattori
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
authors: Hitomi
authors: H
authors: Tsuji
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
authors: Megumi
authors: M
authors: Nukui
authors: Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
authors: Takeshi
authors: T
authors: Inoue
authors: Department of Pediatric Electrophysiology, Osaka City General Hospital, Osaka, Japan.
authors: Yoko
authors: Y
authors: Yoshida
authors: Department of Neurosurgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Takehiro
authors: T
authors: Uda
authors: Department of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors: Sadami
authors: S
authors: Kimura
authors: Department of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors: Yukiko
authors: Y
authors: Mogami
authors: Department of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors: Yasuhiro
authors: Y
authors: Suzuki
authors: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors: Nobuhiko
authors: N
authors: Okamoto
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Biochemistry, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors: Hirotomo
authors: H
authors: Saitsu
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Naomichi
authors: N
authors: Matsumoto
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D000081033:Potassium Channels, Sodium-Activated; D011802:Quinidine / Q000627:therapeutic use*; D013036:Spasms, Infantile / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; C585122:KCNT1 protein, human; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; D011802:Quinidine
keywords: Children; Epileptic encephalopathy; Epileptic spasms; Potassium channel; Treatment