Genotypes and phenotypes of IQSEC2 gene variants related epilepsy.
10.3760/cma.j.cn112140-20220614-00550
- VernacularTitle:IQSEC2基因变异相关癫痫基因型与临床表型特点
- Author:
Dian Hui WANG
1
;
Xue Yang NIU
1
;
Miao Miao CHENG
1
;
Yi CHEN
1
;
Ying YANG
1
;
Xiao Ling YANG
1
;
Zhi Xian YANG
1
;
Yue Hua ZHANG
1
Author Information
1. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
- Publication Type:Journal Article
- MeSH:
Female;
Male;
Child;
Humans;
Spasms, Infantile/genetics*;
Genotype;
Phenotype;
Epilepsy/genetics*;
Seizures;
Spasm;
Guanine Nucleotide Exchange Factors
- From:
Chinese Journal of Pediatrics
2022;60(12):1317-1321
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To analyze the genotypes and clinical phenotypes of patients with epilepsy associated with IQSEC2 gene variants. Methods: The genotypes, seizure types, electroencephalogram, neuroimage of 6 patients with IQSEC2 gene variants in the Department of Pediatrics, Peking University First Hospital from July 2019 to October 2021 were analyzed. Results: There were 5 males and 1 female. Six variants were de novo, including 2 frameshift variants (c.3801_3808dup/p.Q1270Rfs*130, c.1459_1460delAT/p.M487Vfs*2), 2 nonsense variants (c.3163C>T/p.R1055*, c.1417G>T/p.E473*), 1 in-frame deletion (c.2295_2297del/p.N765del) and 1 missense variant (c.2293A>G/p.N765D). Age at seizure onset ranged from 3 months to 2 years and 5 months. Multiple seizure types were observed, including epileptic spasms in 5 patients, focal seizures in 5 patients, tonic seizures in 3 patients, myoclonic seizures in 3 patients, atypical absence seizures in 2 patients and atonic seizures in 2 patients. All 6 patients showed global developmental delay before seizure onset. There were other clinical manifestations, including autistic features in 3 patients, microcephaly in 3 patients, dystonia in 2 patients and binocular esotropia in 1 patient. The electroencephalogram showed slow background activity and hypsarrhythmia in all 6 patients. Brain magnetic resonance imaging showed abnormal in 5 patients and normal in 1 patient. Five patients were diagnosed with infantile spasms. Among them, 4 patients had late-onset infantile spasms. One patient was unclassified developmental epileptic encephalopathy. The age of last follow-up ranged from 3 years and 2 months to 7 years and 2 months. All 6 patients still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset of patients with IQSEC2 gene variants usually begins after 1 year of age. The common seizure types include epileptic spasms and focal seizures. Patients usually have a global developmental delay before seizure onset. IQSEC2 variants could be related to developmental and epileptic encephalopathy, and most patients are diagnosed with late onset infantile spasms. Epilepsy associated with IQSEC2 gene variants is usually refractory.
