Abstract：
BACKGROUND: Voltage-gated sodium channels are involved in the initial depolarisation of neurones. As such, they play important roles in neurotransmission. Variants in the genes encoding these channels may lead to altered functionality and neurodevelopmental disorders. Pathogenic variants of SCN8A, which encodes the voltage-gated Na+ channel Nav1.6, have been associated with various encephalopathies characterised by developmental delay and epileptic seizures. Herein, we discuss the genotype-phenotype associations in a group of 17 novel Polish patients with SCN8A mutations, further expanding the molecular and phenotypic spectrum of SCN8A-related diseases.
METHODS: The participants were recruited from five clinical centres in Poland. Pathogenic and likely pathogenic SCN8A variants were identified using a next-generation sequencing (NGS) panel and exome sequencing, respectively. Magnetic resonance imaging (MRI) and electroencephalography (EEG) recordings were performed to obtain relevant clinical data on brain malformations and epileptic seizures.
RESULTS: Three phenotypes were observed in the study group: developmental and epileptic encephalopathy, early onset epileptic encephalopathy, and neurodevelopmental disorders without epilepsy. Patients in the first two phenotypic subgroups presented with epileptic seizures within the first few months of life. Their semiology evolved with age, comprising mostly tonic, clonic, and tonic-clonic seizures, with eyelid myoclonia, myoclonic seizures, and epileptic spasms. The most prevalent neurological feature was developmental delay. Alterations in muscle tone were more frequent than in previous reports.
CONCLUSIONS: Seventeen patients with 11 novel mutations in SCN8A had alterations in muscular tone accompanied by typical features of SCN8A-related encephalopathies (i.e., developmental delay and a wide range of seizures).
METHODS: The participants were recruited from five clinical centres in Poland. Pathogenic and likely pathogenic SCN8A variants were identified using a next-generation sequencing (NGS) panel and exome sequencing, respectively. Magnetic resonance imaging (MRI) and electroencephalography (EEG) recordings were performed to obtain relevant clinical data on brain malformations and epileptic seizures.
RESULTS: Three phenotypes were observed in the study group: developmental and epileptic encephalopathy, early onset epileptic encephalopathy, and neurodevelopmental disorders without epilepsy. Patients in the first two phenotypic subgroups presented with epileptic seizures within the first few months of life. Their semiology evolved with age, comprising mostly tonic, clonic, and tonic-clonic seizures, with eyelid myoclonia, myoclonic seizures, and epileptic spasms. The most prevalent neurological feature was developmental delay. Alterations in muscle tone were more frequent than in previous reports.
CONCLUSIONS: Seventeen patients with 11 novel mutations in SCN8A had alterations in muscular tone accompanied by typical features of SCN8A-related encephalopathies (i.e., developmental delay and a wide range of seizures).
摘要：
背景：电压门控钠通道参与神经元的初始去极化。因此，它们在神经传递中起重要作用。编码这些通道的基因变异可能导致功能改变和神经发育障碍。SCN8A的致病变异，编码电压门控Na通道Nav1.6，与以发育迟缓和癫痫发作为特征的各种脑病有关。在这里，我们讨论了一组17个新的波兰患者SCN8A突变的基因型-表型关联，进一步扩大SCN8A相关疾病的分子和表型谱。
方法：参与者来自波兰的五个临床中心。使用下一代测序（NGS）小组和外显子组测序鉴定致病性和可能致病性SCN8A变体，分别。进行磁共振成像（MRI）和脑电图（EEG）记录，以获得有关脑畸形和癫痫发作的相关临床数据。
结果：在研究组中观察到三种表型：发育性脑病和癫痫性脑病，早发性癫痫性脑病,和没有癫痫的神经发育障碍。前两个表型亚组的患者在生命的最初几个月内出现癫痫发作。他们的符号学随着年龄的增长而发展，主要包括补品，克隆人,强直-阵挛性癫痫发作,有眼睑肌阵挛症，肌阵挛性癫痫发作,癫痫性痉挛.最普遍的神经系统特征是发育迟缓。肌肉张力的改变比以前的报告更频繁。
结论：17例SCN8A有11个新突变的患者肌肉张力改变，伴有SCN8A相关脑病的典型特征（即，发育迟缓和广泛的癫痫发作)。
方法：参与者来自波兰的五个临床中心。使用下一代测序（NGS）小组和外显子组测序鉴定致病性和可能致病性SCN8A变体，分别。进行磁共振成像（MRI）和脑电图（EEG）记录，以获得有关脑畸形和癫痫发作的相关临床数据。
结果：在研究组中观察到三种表型：发育性脑病和癫痫性脑病，早发性癫痫性脑病,和没有癫痫的神经发育障碍。前两个表型亚组的患者在生命的最初几个月内出现癫痫发作。他们的符号学随着年龄的增长而发展，主要包括补品，克隆人,强直-阵挛性癫痫发作,有眼睑肌阵挛症，肌阵挛性癫痫发作,癫痫性痉挛.最普遍的神经系统特征是发育迟缓。肌肉张力的改变比以前的报告更频繁。
结论：17例SCN8A有11个新突变的患者肌肉张力改变，伴有SCN8A相关脑病的典型特征（即，发育迟缓和广泛的癫痫发作)。
