Clinical Characteristics And Genetics Analysis Of 78 Children With Epileptic Encephalopathy

Objective: To explore the clinical characteristics of children epileptic encephalopathy and to study its genetic characteristics.To provide theoretical support and laboratory basis for further understanding of epileptic encephalopathy and its genetic etiology.Methods: A total of 78 children with epileptic encephalopathy who were diagnosed in the Department of Neurology of Hebei Children’s Hospital from January 2019 to June 2020 were selected as the research subjects.Firstly,the clinical characteristics were analyzed retrospectively,and the genetic characteristics of the children were detected by the second generation gene sequencing method.Results:1.The male-female ratio of the 78 children with epileptic encephalopathy was 1:1.11(41 girls and 37 boys),and the majority(65.38%)of the children were over 1 year old.The onset age of 88.46%(69/78)children was in infancy(0-3 years old).2.Birth history was collected from 65 children,of which 13 were abnormal,and the abnormal rate of birth history was 20.00%;Family genetic history was collected from 71 children,and the results showed that there were20 cases with family history,accounting for 25.64% of all children.A total of69 children were examined for development(Gesell intelligence test for children at 0-6 years old,Wechsler intelligence Scale for children over 6 years old),of which 52 were abnormal,with an abnormal rate of 75.36%.Most of the children had one or more of the mental retardation,cognitive impairment,language impairment,personal social interaction,fine motor impairment,and major motor impairment,among which multiple disorders were the main ones.A total of 72 children were examined by electroencephalogram.Among them,67 cases had abnormal EEG,the abnormal rate of EEG was 93.06%.A total of66 children underwent cranial MRI.Among them,11 cases were abnormal in cranial MRI,with an abnormal rate of 16.6%.3.The types of epileptic seizures in 78 children with epileptic encephalopathy were diversified,including 15 cases of focal seizures(19.23%),13 cases of general tonic clonus(16.67%),13 cases of spasticity(16.67%),12 cases of tonic seizures(15.38%),6 cases of clonic seizures(7.69%),5 cases(6.41%)of focal secondary generalized seizures,5 cases of absence seizures(6.41%),19 cases of other(non-specific)(24.36%).4.A total of 54 pathogenic or possibly pathogenic mutations were detected in 53 children,among which one child carried two possible pathogenic mutations.The 54 pathogenic or potentially pathogenic mutations were distributed in 23 genes,including 9 genes in more than 2 patients,including SCN1A(11 cases),KCNQ2(7 cases),PCDH19(5 cases),SCN2A(4 cases),SCN9A(2 cases),KCNT1(2 cases),SCN8A(2 cases),GRIN2A(2cases),DEPDC5(2 cases),and CHD2(2 cases).One patient showed(possibly)pathogenic mutation in each of the remaining 15 genes,and the 15 genes were as follows: PACS2,DNM1,TSC2,CDKL5,CYFIP2,OTC,PRRT2,SCN1 B,GABRA1,TBC1D24,SYNGAP1,GABRB3,SYNGAP1,CRIN2 D,and SZT2.Among them,the proportion of new-born mutations was 87.04%(47/54),and the proportion of inherited mutations from relatives was 12.96%(7/54).The proportion of missense mutations was 79.63%(43/54),the proportion of frameshift mutations was 9.26%(5/54),the proportion of nonsense mutations was 5.56%(3/54),and the proportion of deletion mutations It was 3.70%(2/54),1 case of splicing mutation,accounting for 1.85%.5.Among the genes with different functions,the gene encoding ion channel had the largest number of mutations,accounting for 57.41%(31/54)of all disease-causing or possibly disease-causing mutations,among which SCN1 A gene ranked the first(11/54).The number of mutations in the calcium-dependent adhesion protein genes accounted for 9.26%(5/54)of all the genes that caused or might cause disease.Conclusions:1.There may be no significant gender difference in epileptic encephalopathy.Most of them are at a low age,and a considerable proportion of the children have a long course of disease after the onset,or the disease progresses continuously.2.Abnormal birth history and a family history of neurological diseases may be associated with epileptic encephalopathy.3.The high rate of abnormal detection in children with epileptic encephalopathy,suggesting that genetic factors are important influencing factors in the occurrence of disease.4.In this study,54 pathogenic or possible pathogenic gene mutations were found,which were distributed in 24 genes.Ion channel gene mutation is the most important type of gene mutation.