Analysis of characteristics and phenotypes of SCN1A and SCN2A gene mutations in children with epilepsy with febrile seizures
Objective To explore and analyze the phenotypic characteristics and genotypes of children with epilepsy with febrile sei-zures associated with SCN1A and SCN2A gene mutations.Methods The clinical data of 56 children with epilepsy and febrile seizures who underwent genetic screening and were followed up in department of pediatrics of the Shanghai Sixth People's Hospital(Lingang Hospital District)were retrospectively selected from June 2020 to January 2022.Venous whole blood of all children and their parents were collected for gene sequencing to find suspected pathogenic mutations.Sanger sequencing was used to verify the sources of gene mutations.The clinical characteristics,clinical phenotyping,treatment regimen method,prognosis and gene mutations were compared between children with SCN1A and SCN2A gene mutations.Results Among the 56 children,42 cases were negative and 14 cases were positive by gene test,including 7 cases of simple SCN1A gene mutation,6 cases of simple SCN2A gene mutation and 1 case of both SCN1A and SCN2A mutations.Among the 14 cases with gene mutations,6 cases were males and 8 cases were females,with the age of onset from 2 days to 2 years and 7 months and the treatment age from 1 month to 3 years old.The clinical features were shown as men-tal retardation in 11 cases(mild in 7 cases,moderate in 4 cases),mild neurodevelopmental retardation in 2 cases and mild language re-tardation in 1 case.Clinical phenotypes were manifested as febrile seizure plus in 9 cases,Dravet syndrome in 3 cases,infantile spasm in 1 case and early-onset epileptic encephalopathy in 1 case.The seizure types were expressed as 6 cases of clonic seizure,4 cases of tonic seizure,2 cases of tension loss,1 case of tonic-clonic seizure and 1 case of loss of consciousness.The seizure frequency ranged from 8-12 times a day to 5-8 times a month,and the duration from tens of seconds to 2 to 3 minutes and the treatment regimen was with valproic acid,levetiracetam,topiramate,topamax,oxcarbazepine,nitrazepam and prednisone alone or in combination.The seizures were controlled in 8 cases and reduced in 6 cases after treatment.Among the 14 children with gene mutations,there were 7 cases of SCN1A mutation with the main mutation site of Chr2,including 5 cases of missense mutation,1 case of frameshift mutation and 1 case of shear site mutation;there were 5 cases of autosomal dominant inheritance and 2 cases of X chromosome inheritance;there were 4 cases from the mother,2 cases from the father and 1 case from the newborn.6 cases were with SCN2A mutation with the main mutation site of Chr2,including 4 cases of missense mutation,1 case of frameshift mutation and 1 case of non-coding region mutation;all cases were autosomal dominant inheritance;there were 2 cases from the mother,1 case from the father and 3 cases from the newborn.1 case was with SCN1A and SCN2A mutations,with the mutation type of missense mutation.Conclusions SCN1A and SCN2A gene muta-tions are mainly missense mutations,which are mainly caused by de novo mutations and genetic mutations,with clinical manifestations as mostly febrile seizure plus.SCN1A and SCN2A genes can be used as effective targets for early clinical prevention and treatment of epilepsy with febrile seizures.
万方数据
维普
