Cohort of Phenotype, Genotype, and Outcome of SCN Developmental and Epileptic Encephalopathies from Southern Part of India.

IF 0.4 Q4 PEDIATRICS
Vykuntaraju K Gowda, Manojna Battina, Hemadri Vegda, Varunvenkat M Srinivasan, Surendra K Chikara, Adrija Mishra, Sanjay K Shivappa, Naveen Benakappa
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引用次数: 1

Abstract

The SCN encephalopathies are one of the rare early childhood intractable epileptic encephalopathies associated with pleomorphic seizures, cognitive decline, motor, and behavioral abnormalities that begin in early infancy. There is a dearth of data on phenotype and genotype of SCN encephalopathies from the Indian subcontinent, hence we are reporting clinical and molecular profile and outcome of SCN developmental and epileptic encephalopathies. This is a retrospective chart review of SCN developmental and epileptic encephalopathies in a tertiary care center, Bangalore, India between January 2015 and March 2020. All children with clinical features of SCN developmental and epileptic encephalopathies and confirmed with pathogenic variants were included. A total of 50 cases of SCN developmental and epileptic encephalopathies were analyzed, 31 of them were male and the mean age of presentation was 7.8 months. Precipitating factors for the first episode of seizure were fever and vaccination accounting for 33 and 8 children, respectively. Forty (80%) children had prolonged seizures and 15 (30%) had epileptic spasms. All children had a normal birth history and normal development before the onset of seizures, which was followed by developmental delay and regression. Thirty (60%) children had behavioral difficulties, notable hyperactivity, and autistic features. Neuroimaging and the initial electroencephalogram (EEG) were normal in all patients. The mean age of abnormal EEG was 14 months. The various subtypes of SCN variants were SCN1A in 31 children followed by SCN2A and SCN9A in eight children each and SCN1B in three children. Frameshift and nonsense mutations were associated with more severe phenotype and poor outcome compared with missense mutations. Thirty-four patients partially responded to treatment and the rest were refractory. The results of genetic testing were used to guide treatment; sodium channel blocking antiepileptic drugs were discontinued in 15 patients and sodium channel blocking agents were started in 3 patients with partial response. Three out of four children on stiripentol had a partial response. The SCN developmental and epileptic encephalopathies can present with epileptic spasms in addition to other types of seizures. Epileptic spasms are more common in nonsense and frameshift mutations. The outcome is poor in children with epileptic spasms compared with those without epileptic spasms. Genetic testing helps to select antiepileptic drugs that lead to seizure reduction.

印度南部SCN发育性和癫痫性脑病的表型、基因型和预后队列研究
SCN脑病是一种罕见的早期儿童顽固性癫痫性脑病,与婴儿期早期开始的多形性癫痫发作、认知能力下降、运动和行为异常有关。由于缺乏来自印度次大陆的SCN脑病的表型和基因型数据,因此我们报告SCN发育性和癫痫性脑病的临床和分子特征和结果。这是2015年1月至2020年3月期间印度班加罗尔三级保健中心SCN发育性和癫痫性脑病的回顾性图表综述。所有具有SCN发育性和癫痫性脑病临床特征并确诊为致病变异的儿童均被纳入研究。本文分析50例SCN发育性和癫痫性脑病,其中31例为男性,平均发病年龄为7.8个月。首次发作的诱发因素为发热和接种疫苗,分别占33例和8例。40例(80%)儿童有长时间癫痫发作,15例(30%)有癫痫性痉挛。所有患儿在癫痫发作前均有正常的出生史和发育,随后出现发育迟缓和倒退。30名(60%)儿童有行为困难、明显的多动和自闭特征。所有患者的神经影像学和初始脑电图均正常。异常脑电图的平均年龄为14个月。SCN变异的各种亚型分别为:31名儿童的SCN1A, 8名儿童的SCN2A和SCN9A, 3名儿童的SCN1B。与错义突变相比,移码突变和无义突变与更严重的表型和更差的预后相关。34例患者对治疗有部分反应,其余患者难治性。基因检测结果用于指导治疗;15例患者停用钠通道阻断类抗癫痫药物,3例患者开始使用钠通道阻断类抗癫痫药物。四分之三的服用斯瑞喷妥的儿童有部分反应。SCN发育性和癫痫性脑病除了其他类型的癫痫发作外,还可以表现为癫痫性痉挛。癫痫痉挛在无意义和移码突变中更为常见。与没有癫痫性痉挛的儿童相比,癫痫性痉挛儿童的预后较差。基因检测有助于选择减少癫痫发作的抗癫痫药物。
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来源期刊
自引率
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32
期刊介绍: The Journal of Pediatric Genetics is an English multidisciplinary peer-reviewed international journal publishing articles on all aspects of genetics in childhood and of the genetics of experimental models. These topics include clinical genetics, molecular genetics, biochemical genetics, medical genetics, dysmorphology, teratology, genetic counselling, genetic engineering, formal genetics, neuropsychiatric genetics, behavioral genetics, community genetics, cytogenetics, hereditary or syndromic cancer genetics, genetic mapping, reproductive genetics, fetal pathology and prenatal diagnosis, multiple congenital anomaly syndromes, and molecular embryology of birth defects. Journal of Pediatric Genetics provides an in-depth update on new subjects and current comprehensive coverage of the latest techniques used in the diagnosis of childhood genetics. Journal of Pediatric Genetics encourages submissions from all authors throughout the world. The following articles will be considered for publication: editorials, original and review articles, short report, rapid communications, case reports, letters to the editor, and book reviews. The aim of the journal is to share and disseminate knowledge between all disciplines in the field of pediatric genetics. This journal is a publication of the World Pediatric Society: http://www.worldpediatricsociety.org/ The Journal of Pediatric Genetics is available in print and online. Articles published ahead of print are available via the eFirst service on the Thieme E-Journals platform.
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