Clinical Characteristics And Genetic Analysis Of Benign Infantile Convulsions Associated With Mild Gastroenteritis

ObjectAnalyze the clinical data and genetic test results of Benign infantile convulsions associated with mild gastroenteritis,summarize the clinical characteristics of CwG patients,and screen out possible pathogenic genes that may cause CWG.To Explore the clinical significance of gene mutations and clinical phenotypes,and to provide a basis for CwG diagnosis,treatment and genetic counseling.Methods1.Design a clinical data collection form to collect basic information,medical history data,auxiliary examinations,and treatment of 45 patients diagnosed with CwG in Qilu Hospital of Shandong University from 2017.01 to 2020.12.2.Analyze the clinical data of the patients,follow up for over 6 months months,and compare the differences in clinical manifestations between relapsed and non-relapsed patients.3.Perform whole-exome high-throughput gene sequencing on 15 children who underwent genetic testing voluntarily,and their parents used Sanger sequencing for verification,collected the test results,and used PROVE AN,Poly Phen₂,MutationTaster protein function prediction software combined with clinical data to complete the pathogenic analysis.4.Statistical analysis was performed using SPSS 25.0.Categorical variables is expressed by frequency（n）or composition ratio（%）,and the Chi-square test or Fisher’s precision probability test is used to compare two or more groups.Continuous variables are tested for normal distribution and homogeneity of variance.Data conforming to the normal distribution and homogeneity of variance are expressed as mean±standard deviation（x-±s）,and the two groups are compared by t-test;measurement data not conforming to the normal distribution are expressed as the median（interquartile range）,the Mann-Whitney U test was used to compare the two groups.P<0.05 was statistically significant.Results1.General information:This study included 45 CwG patients,11（24.4%）males,34（75.6%）females,female:male=3.1:1.Onset time was autumn（September-November）in 20 cases（44.4%）and winter（December-February）in 15 cases（33.3%）.The age of onset was 5-46 months,of which 35 cases（77.8%）were 13-24 months old.2.Gastroenteritis:Among the 45 patients,only 7 cases（15.6%）had diarrhea,only 10 cases（22.2%）had vomiting,and 28 cases（62.2%）had both diarrhea and vomiting.Diarrhea 1-6 times a day,an average of 3.04±1.50 times;vomiting 1-10 times a day,an average of 4.57± 3.20 times.3.Seizures:epileptic seizures:（1）focal seizures in 4 cases（8.9%）,（2）general tonic seizures in 13 cases（28.9%）,（3）general tonic-clonic seizures in 24 cases（53.3%）,（4）4 cases（8.9%）with focal expansion to bilateral tonic-clonic seizures.The interval between gastroenteritis and seizures was 1-120 hours,15 cases（33.3%）1-24 hours,21 cases（46.7%）25-48 hours,6 cases（13.3%）49-72 hours,3 cases>72 hours（6.7%）;The duration was 10-600 seconds,of which 22 cases（48.9%）were 10-120 seconds,19 cases（42.2%）were 121-300 seconds,and 4 cases（8.9%）were≥300 seconds.The frequency of seizure was 1-10 times within 24 hours.11 patients（24.4%）had non-cluster seizure,and 34 patients（75.6%）had cluster seizure.Among the patients with cluster attacks,16 cases（35.6%）had two episodes,11 cases（24.4%）had three episodes,2 cases（4.4%）had four episodes,1 case（2.2%）had five episodes,3 cases（6.7%）had six episodes,and 1 case（2.2%）had 10 episodes.4.Among the 45 patients,the Na+test results of 20 patients（44.4%）were lower than the lower limit of the reference range;The AST test results of 32 patients（71.1%）exceeded the upper limit of the reference range.5.Comparison of clinical characteristics of patients with and without recurrence:Overall,there was no statistically significant difference between the two groups in age of onset,interval time,types of seizures,number of seizures,and duration of seizures（P>0.05）;Pair comparison showed that the onset age of children ≤1 years old was different between the two groups,suggesting that the onset age of children≤1 years old was more likely to relapse6.In 14 of the 15 children,mutations associated with seizures were detected in 17 different genes,including:Gnao1,KCNQ2,KCNA2,SETD1B,CYFIP2,KCNQ3,CACNA1E,FGF12,GRIN2D,PRRT2,KCNT2,KCNH1,SCN8A,CNNM2,CACNA1A,L2HGDH,MMUT.There were 3 possible pathogenic mutated genes:SCN8A,CNNM2 and CACNA1A.Among them,L2HGDH and MMUT were autosomal recessive complex heterozygous mutations.No pathogenic variation was found.Conclusions1.CwG mainly occurs in autumn and winter,most within 2 years old,and usually occurs within 48 hours after gastroenteritis symptoms.2.The type of seizure is mainly generalized,clustered;it may be accompanied with mild hyponatremia and non-specific elevated AST.3.Patients younger than 1 year old are prone to relapse.4.SCN8A and CNNM2 are genes that may be related to CwG,which broadens the gene phenotype spectrum;L2HGDH and MMUT gene mutations may cause clinical phenotypes similar to CwG,so attention should be paid to the identification.