Makiko Saitoh1, Atsushi Ishii2, Yukiko Ihara2, Ai Hoshino3, Hiroshi Terashima4, Masaya Kubota4, Kenjiro Kikuchi5, Gaku Yamanaka6, Kaoru Amemiya7, Shinichi Hirose2, Masashi Mizuguchi3. 1. Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: makisaito-tky@umin.ac.jp. 2. Department of Pediatrics, Fukuoka University, Fukuoka, Japan. 3. Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 4. Division of Neurology, National Center for Child Health and Development, Tokyo, Japan. 5. Division of Neurology, Saitama Children's Medical Center, Saitama, Japan. 6. Department of Pediatrics, Tokyo Medical University, Tokyo, Japan. 7. Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
Abstract
OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood encephalopathy following severe febrile seizures. The pathogenesis of AESD is considered to be fever-induced seizure susceptibility and excitotoxicity, which may be caused by sodium channel dysfunction in some cases. Here we studied whether mutations in genes encoding sodium channels, SCN1A and SCN2A, predispose children to AESD. METHODS: We recruited 92 AESD patients in a nationwide survey of acute encephalopathy in Japan from 2008 to 2011. We collected their genomic DNA samples, and sequenced the entire coding region of SCN1A and SCN2A. RESULTS: Five out of 92 patients (5.4%) had missense mutations either in SCN1A or SCN2A. After a preceding infection with fever, all the patients showed status epilepticus at the onset. Hemiconvulsion-hemiplegia was recognized in three patients during the acute/subacute phase. One patient had taken theophylline for the treatment of bronchial asthma just before the onset of AESD. Familial history was not remarkable except one patient with a SCN1A mutation (G1647S) whose mother had a similar episode of AESD in her childhood. A different substitution (G1674R) at the same amino acid position, as well as two other SCN1A mutations found in this study, had previously been reported in Dravet syndrome. Another SCN1A mutation (R1575C) had been detected in other types of acute encephahlitis/encephalopathy. One patient had SCN2A mutation, F328V, which had previously been reported in Dravet syndrome. Another SCN2A mutation, I172V, was novel. None of the patients were diagnosed with Dravet syndrome or genetic (generalized) epilepsy with febrile seizure plus in the following-up period. CONCLUSIONS: Mutations in SCN1A and SCN2A are a predisposing factor of AESD. Altered channel activity caused by these mutations may provoke seizures and excitotoxic brain damage.
OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood encephalopathy following severe febrile seizures. The pathogenesis of AESD is considered to be fever-induced seizure susceptibility and excitotoxicity, which may be caused by sodium channel dysfunction in some cases. Here we studied whether mutations in genes encoding sodium channels, SCN1A and SCN2A, predispose children to AESD. METHODS: We recruited 92 AESDpatients in a nationwide survey of acute encephalopathy in Japan from 2008 to 2011. We collected their genomic DNA samples, and sequenced the entire coding region of SCN1A and SCN2A. RESULTS: Five out of 92 patients (5.4%) had missense mutations either in SCN1A or SCN2A. After a preceding infection with fever, all the patients showed status epilepticus at the onset. Hemiconvulsion-hemiplegia was recognized in three patients during the acute/subacute phase. One patient had taken theophylline for the treatment of bronchial asthma just before the onset of AESD. Familial history was not remarkable except one patient with a SCN1A mutation (G1647S) whose mother had a similar episode of AESD in her childhood. A different substitution (G1674R) at the same amino acid position, as well as two other SCN1A mutations found in this study, had previously been reported in Dravet syndrome. Another SCN1A mutation (R1575C) had been detected in other types of acute encephahlitis/encephalopathy. One patient had SCN2A mutation, F328V, which had previously been reported in Dravet syndrome. Another SCN2A mutation, I172V, was novel. None of the patients were diagnosed with Dravet syndrome or genetic (generalized) epilepsy with febrile seizure plus in the following-up period. CONCLUSIONS: Mutations in SCN1A and SCN2A are a predisposing factor of AESD. Altered channel activity caused by these mutations may provoke seizures and excitotoxic brain damage.
Authors: Jennifer C Wong; Kameryn M Butler; Lindsey Shapiro; Jacquelyn T Thelin; Kari A Mattison; Kathryn B Garber; Paula C Goldenberg; Shobana Kubendran; G Bradley Schaefer; Andrew Escayg Journal: Front Pharmacol Date: 2021-11-17 Impact factor: 5.988