Abstract：
OBJECTIVE: HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies.
METHODS: Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay.
RESULTS: In this study, eight de novo variants of HCN1 genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic-clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay.
CONCLUSIONS: Our research reported eight variants in HCN1 gene causing epilepsy; among these variants, five variants were never reported before. HCN1-related epilepsy usually starts infantile period, and focal secondary generalized tonic-clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for HCN1-related epilepsy.
METHODS: Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay.
RESULTS: In this study, eight de novo variants of HCN1 genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic-clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay.
CONCLUSIONS: Our research reported eight variants in HCN1 gene causing epilepsy; among these variants, five variants were never reported before. HCN1-related epilepsy usually starts infantile period, and focal secondary generalized tonic-clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for HCN1-related epilepsy.
摘要：
目的：HCN离子通道家族在神经元中广泛表达，最近越来越多的研究表明了它们在癫痫中的作用。
方法：在一项回顾性研究中收集了患者的临床资料。外显子测序用于无法解释的复发性癫痫发作和不同程度的发育迟缓的患者。
结果：在这项研究中，在八名患者中发现了八种HCN1基因的从头变异，包括六个错觉变体，一个无义变体和一个移码插入变体，其中五个是第一次报告。八名患者的发病年龄从一个月到一年不等。其主要临床表现为癫痫和不同程度的发育迟缓,发作的主要类型是局灶性继发性全身强直-阵挛性发作。重要的是,在我们的研究中,1例出现了一种未在文献中报道的转移性局灶性癫痫发作.8名儿童中有5名儿童的癫痫发作得到了包括丙戊酸在内的抗癫痫药物的有效控制，左乙拉西坦和奥卡西平。一个孩子发育正常，四个孩子发育轻度延迟。一个孩子接受了托吡酯治疗,惊厥得到部分控制，表现为中度至重度发育迟缓。另外两个孩子的抗癫痫治疗失败了，两个孩子接受了丙戊酸钠治疗，奥卡西平,拉莫三嗪,氯巴赞,左乙拉西坦和硝基地西泮连续，但他们的惊厥没有得到控制，表现为中度至重度发育迟缓。
结论：我们的研究报道了导致癫痫的HCN1基因的八种变异，在这些变体中，以前从未报道过5种变体.HCN1相关的癫痫通常开始婴儿期，局灶性继发性全身强直-阵挛性发作是最常见的发作类型。重要的是,我们报告的病例很少报告为转移性局灶性癫痫.我们的研究扩展了HCN1相关癫痫的基因型和表型。
方法：在一项回顾性研究中收集了患者的临床资料。外显子测序用于无法解释的复发性癫痫发作和不同程度的发育迟缓的患者。
结果：在这项研究中，在八名患者中发现了八种HCN1基因的从头变异，包括六个错觉变体，一个无义变体和一个移码插入变体，其中五个是第一次报告。八名患者的发病年龄从一个月到一年不等。其主要临床表现为癫痫和不同程度的发育迟缓,发作的主要类型是局灶性继发性全身强直-阵挛性发作。重要的是,在我们的研究中,1例出现了一种未在文献中报道的转移性局灶性癫痫发作.8名儿童中有5名儿童的癫痫发作得到了包括丙戊酸在内的抗癫痫药物的有效控制，左乙拉西坦和奥卡西平。一个孩子发育正常，四个孩子发育轻度延迟。一个孩子接受了托吡酯治疗,惊厥得到部分控制，表现为中度至重度发育迟缓。另外两个孩子的抗癫痫治疗失败了，两个孩子接受了丙戊酸钠治疗，奥卡西平,拉莫三嗪,氯巴赞,左乙拉西坦和硝基地西泮连续，但他们的惊厥没有得到控制，表现为中度至重度发育迟缓。
结论：我们的研究报道了导致癫痫的HCN1基因的八种变异，在这些变体中，以前从未报道过5种变体.HCN1相关的癫痫通常开始婴儿期，局灶性继发性全身强直-阵挛性发作是最常见的发作类型。重要的是,我们报告的病例很少报告为转移性局灶性癫痫.我们的研究扩展了HCN1相关癫痫的基因型和表型。
