ABSTRACT
Objective@#To analyze the clinical characteristics and gene mutations of early-onset epileptic encephalopathy(EOEE) caused by ion channel gene mutation, to identify the etiology, to guide the treatment and to provide the basis for genetic counseling.@*Methods@#The clinical data from 17 children with EOEE caused by ion channel gene mutation and the peripheral blood of the children and their parents were collected from June 2014 to May 2018 at the Department of Neurology, Tianjin Children′s Hospital.Epilepsy gene sequencing was performed by using disease gene targeting second generation sequencing technology.The mutation of pathogenic ion channel gene was found.The confirmed mutations were verified by Sanger sequencing and the source of the mutation was identified.@*Results@#Among 17 case with EOEE, 3 cases had genetic mutation, and 14 cases had denovo mutations.Dravet syndrome was found in 8 cases (47.1%), there were SCN1A gene missense mutation in 5 cases, SCN1A gene nonsense mutation in 3 cases, KCNQ2 gene missense mutation in 1 case (5.9%) and non-specific epileptic encephalopathy in 8 cases (47.1%). SCN2A gene missense mutation, SCN4A gene missense mutation, SCN8A gene missense mutation, KCNQ2 gene missense mutation and KCNH gene missense mutation were found in suspected pathogenic mutations.There were 1 missense mutation out of 5 genes, 1 missense mutation of CACNA1A gene, 1 missense mutation of GRIN2A gene and 1 missense mutation of GRIN3A gene.Seventeen patients were treated with 2 or more antiepileptic drugs, 4 with ketogenic diet and 1 with vitamin B6 supplementation.During 11 to 96 months of follow-up, seizures were completely controlled in 3 cases (17.6%), decreased in 7 cases (41.2%) by more than 50%, and decreased in 7 cases (41.2%) by less than 50%.@*Conclusions@#The clinical phenotypes for children with unexplained EOEE are varied, and gene mutations of ion cha-nnel are most common.Some gene sites are denovo mutations which have not been reported such as missense mutation for 3 case SCN1A gene, 1 case SCN2A gene, 1 case CACNA1A gene, 1 case KCNH5 gene, and nonsense mutation for 2 case SCN1A gene, which have enriched the mutation spectrum of EOEE.
ABSTRACT
Objective To analyze the clinical characteristics and gene mutations of early －onset epileptic encephalopathy(EOEE)caused by ion channel gene mutation,to identify the etiology,to guide the treatment and to pro﹣vide the basis for genetic counseling. Methods The clinical data from 17 children with EOEE caused by ion channel gene mutation and the peripheral blood of the children and their parents were collected from June 2014 to May 2018 at the Department of Neurology,Tianjin Children′s Hospital. Epilepsy gene sequencing was performed by using disease gene targeting second generation sequencing technology. The mutation of pathogenic ion channel gene was found. The confirmed mutations were verified by Sanger sequencing and the source of the mutation was identified. Results Among 17 case with EOEE,3 cases had genetic mutation,and 14 cases had denovo mutations. Dravet syndrome was found in 8 cases(47. 1﹪),there were SCN1A gene missense mutation in 5 cases,SCN1A gene nonsense mutation in 3 cases, KCNQ2 gene missense mutation in 1 case(5. 9﹪)and non－specific epileptic encephalopathy in 8 cases(47. 1﹪). SCN2A gene missense mutation,SCN4A gene missense mutation,SCN8A gene missense mutation,KCNQ2 gene missense mutation and KCNH gene missense mutation were found in suspected pathogenic mutations. There were 1 missense mu﹣tation out of 5 genes,1 missense mutation of CACNA1A gene,1 missense mutation of GRIN2A gene and 1 missense mu﹣tation of GRIN3A gene. Seventeen patients were treated with 2 or more antiepileptic drugs,4 with ketogenic diet and 1 with vitamin B6 supplementation. During 11 to 96 months of follow－up,seizures were completely controlled in 3 cases (17. 6﹪),decreased in 7 cases(41. 2﹪)by more than 50﹪,and decreased in 7 cases(41. 2﹪)by less than 50﹪. Conclusions The clinical phenotypes for children with unexplained EOEE are varied,and gene mutations of ion cha﹣nnel are most common. Some gene sites are denovo mutations which have not been reported such as missense mutation for 3 case SCN1A gene,1 case SCN2A gene,1 case CACNA1A gene,1 case KCNH5 gene,and nonsense mutation for 2 case SCN1A gene,which have enriched the mutation spectrum of EOEE.
ABSTRACT
Objective To summary the clinical characteristics of epileptic spasm(ES)that is the unique form of seizures in childhood. Methods A total of 149 patients with ES who visited our hospital from May 2009 to June 2015 were collected. The documents of clinical data, treatment and outcome were analyzed retrospectively. The statistical analysis of some clinical characteristics and prognosis of patients were performed. Results There were 97(65.1%) male and 52 (34.9%) female in the 149 patients. The onset age of ES was from 30 days to 42 months (median value was 6 months) including 17 patients more than 12 months.The peak age of onset was 4-7 months. One hundred and forty-seven patients manifested clustered spasm. One pair of twins showed single spasm.Other types of seizure were seen before ES onset in 13 (8.7%) patients, and after ES onset in 42 (28.2%) patients.Eighty-three patients (55.7%) were diagnosed as West syndrome (WS). There were 46 patients (30.9%) with cryptogenic cause, 103 patients (69.1%) diagnosed with symptomatic epilepsy, in which 69 patients were with a clear cause. The proportions of developmental delay in the cryptogenic and symptomatic patients were 74.5% and 92.2% after the onset of the ES. The degree of developmental delay was linearly related to the course of ES. The hyperarrhythmia of electroencephalogram (EEG) background was seen in 122 patients (81.9%), and there was no significant difference in hyperarrhythmia between different etiology groups or different onset age groups. The short-term efficiency of topiramate evaluated within one month was 30.5% in 59 newly diagnosed patients. The short-term effective rate of adrenocorticotropic hormone (ACTH) was 80.3% in total 76 patients, but single ACTH treatment was associated with an increased recurrent rate. Conclusion ES is a highly age dependent seizure type that mainly found in WS,which typically follows a EEG hyperarrhythmia and developmental delay. The treatment of ES is difficult. ACTH combined with effective antiepileptic drugs (AEDS) is currently the most reasonable drug treatment program.
ABSTRACT
Objective To explore the relationship between expression of P-glycoprotein (P-gp), a product of multidrug resistance (MDR) gnne, in the peripheral blood of children with intractable or newly diagnosed epilepsy for drug resistance. To establish a marker of drug resistance. To evaluate the therapeutic effect of flunarizine in the treatment of intractable epileptic patient with or without overexpression of P-gp. Methods The expression of P-gp in peripheral blood were investigated in 86 epileptic children (41 in intractable epilepsy group, 45 in newly diagnosed epilepsy group) and 44 healthy children (controlled group) by flow cytometry. Intractable epileptic patients with or without overexpression of P-gp were given flunarizine 2.5 - 5 mg, po, qn, for 3 months and followed up. Results Overexpression of P-gp were found in 23 (56.1%) patients of intractable epilepsy group, in 10 (22.2%) patients of newly diagnosed epilepsy group and three (6.8%) children of the controlled. In intractable epilepsy group, 17 out of 23 cases (73.9%) patient with overexpression of P-gp became tolerant to antiepileptic drugs, while 3 out of 18 cases (16.7%) patient without expression of P-gp became tolerant to antiepileptic drugs, and there was significant difference between them (P < 0.01) . In the newly diagnosed epilepsy group, seven out of 10 cases (70%) with overexpression of P-gp became intractable epileptic patient and three out of 35 eases (18.6%) without expression of P-gp became intractable epileptic patient, there was significant difference between them (P < 0.01). Twenty patients of intractable epilepsy group were given flunarizine for three months, 11 of 17 patients with P-gp overexpression and 1 of 3.patients without P-gp expression were effective. When reexamined, P-gp expression in 6 out of 11 patients became negative. Conclusions It is suggested that overexpression of P-gp in the peripheral blood of intractable epileptic patients might be a significant marker of drug resistance. Newly diagnosed epileptic patients with overexpression of P-gp may develop intractable epilepsy. P-gp was a predictable marker of intractable epilepsy. Flunarizine could be a choice in treatment of intractable epilepsy with overexpression of P-gp. The antiepileptic mechanism of flunarizine may involve in reversing of P-gp.