A study on genotype and clinical phenotype characteristics of children with epilepsy associated with SCN1B gene variations
10.3760/cma.j.cn113694-20240924-00636
- VernacularTitle:SCN1B基因变异相关癫痫患儿基因型及临床表型特点研究
- Author:
Xiaojing XU
1
;
Ting WANG
1
;
Miaomiao CHENG
1
;
Shijia OUYANG
1
;
Ying YANG
1
;
Xiaoling YANG
1
;
Changhao LIU
1
;
Yuehua ZHANG
1
Author Information
1. 北京大学第一医院儿童医学中心儿童神经内科，北京102699
- Publication Type:Journal Article
- Keywords:
Epilepsy;
SCN1B gene;
Genotype;
Phenotype;
Treatment
- From:
Chinese Journal of Neurology
2025;58(6):624-631
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the genotype and clinical phenotype characteristics of children with epilepsy associated with the SCN1B gene encoding the sodium channel β1 subunit. Methods:The genotypes and clinical phenotypes of patients with SCN1B variants among suspected genetic epilepsy cases treated at the Children′s Medical Center of Peking University First Hospital between May 2016 and July 2024 were analyzed. These variants were identified using next-generation sequencing and subsequently validated by Sanger sequencing or quantitative polymerase chain reaction methods. Results:A total of 17 patients were analyzed, including 8 males and 9 females. Ten cases of missense variations (including 2 with the same variations), 4 cases of deletion variations, and 1 case each of nonsense variations, splice site variations, and exons 4-5 deletions were identified. Among them, 6 cases had novel SCN1B variations. The variants in 11 cases were inherited from 1 parent. Eleven types of gene variants have not been reported yet. Onset of epilepsy ranged from 3 months to 5 years and 3 months old (median age: 14 months). Types of seizures included generalized tonic-clonic seizures (GTCS) in 14 cases, focal seizures in 9 cases, myoclonic seizures in 3 cases, atypical absence seizures in 2 cases and epilepsy spasms, tonic seizures and atonic seizures in 1 case each. Eleven cases had diverse seizure types. Fourteen cases (14/17) demonstrated fever sensitivity. Electroencephalography revealed focal discharges in 3 cases, coinciding with focal and generalized discharges in 3 additional cases, and multifocal discharges in 6 cases. Seizures were identified in 4 cases: 1 case of myoclonic seizures, 1 case of GTCS, 1 case of atypical absence seizures, and 1 case exhibiting both myoclonic and tonic seizures. Nine cases (9/17) were diagnosed with genetic epilepsy with febrile seizures plus, 1 case diagnosed with myoclonic epilepsy in infancy and 1 diagnosed with infant epileptic spasms syndrome. There were 2 cases of nonspecific developmental epileptic encephalopathy, while the remaining 4 cases could not be diagnosed with a specific epileptic syndrome. Effective antiseizure medications (ASMs) included valproate in 8 cases, levetiracetam in 5 cases, topiramate in 3 cases, clobazam in 2 cases, clonazepam and vigabatrin in 1 case each. Sodium channel blockers exacerbated seizures in 3 cases, specifically oxcarbazepine in 2 cases and lamotrigine in 1 case. At the last follow-up, seizures were controlled for at least 6 months in 14 patients (14/17), while seizures remained uncontrolled in 3 patients despite trialing 2 or more ASMs. Thirteen patients exhibited normal development, while 4 experienced developmental delays. Conclusions:The heterozygous variants in children with SCN1B gene-related epilepsy include missense, deletion, nonsense, splice site variants, and exon deletions. The correlation between different genetic variants and clinical phenotypes remains unclear. These variants are associated with epilepsy onset from infancy to early childhood, presenting with various seizure types, with GTCS being the most common. Phenotypic manifestations can vary significantly in severity, ranging from benign febrile seizures or febrile seizures plus to developmental epileptic encephalopathy. Valproic acid demonstrates the highest effectiveness rate, while the use of sodium channel blockers may worsen seizures in certain patients, necessitating cautious administration.
