| Objective: To investigate and analyze the clinical characteristics and gene mutations of children with unexplained infantile spasms.Methods:(1)Clinical data of 22 children with unexplained infantile spasms in the neurological ward from May 2015 to April 2017 in the Children’s Hospital of Chongqing Medical University were analyzed,including general information,medical history,physical examination,metabolic screening,electroencephalogram(EEG),imaging examination,drug treatment,and 9-32 months follow-up for seizures and EEG changes.(2)Using epilepsy-related gene trapping technology combined with second-generation sequencing to analyze epilepsy-related gene sequencing and look for gene mutation,as well as combining clinical data with Polyphen-2 and SIFT software results to predict the pathogenicity of the gene mutations.(3)Comparing clinical characteristics of 5 infants with pathogenic gene mutations and 17 infants without pathogenic gene mutations,including gender,other forms of seizures before onset of spasms,age of onset,spasms type,EEG changes,drug treatment and efficacy,as well as seizures and EEG changes during follow-up.Results:(1)Among these 22 children with unexplained IS in this study,there were 11 males and 11 females;17 children(77.27%)had IS onset with spasms,while 5 children(22.73%)had other seizures before spasms;The age of onset was from 2 days to 27 months after birth,median was 4 months,of whom 8 cases(36.36%)were early-onset IS,13 cases(59.09%)were typical IS,1 case(4.55%)had spasms onset at 27 months,all infants presented with typical spasms,19 cases(86.36%)with flexion-type spasms,1 case(4.55%)with extension-type,2 cases(9.09%)with mixed-type,and about EEG,20 cases(90.91%)had hypsarrhythmia,2 children(9.09%)only had other forms of epileptic discharge waves.(2)Among these 22 children,2 cases(9.09%)preferred hormone therapy,12 cases(54.55%)preferred anti-epilepsy drugs(AEDs)therapy,and 6 cases(27.27%)preferred hormone combined with AED,1 case(4.55%)preferred AED combined with vitamin B6,and 1 case(4.55%)preferred vitamin B6 treatment.One to five(median 2.00,IQR 1.75-3.00)kinds of AEDs were used.A total of 18 patients were successfully followed up from 9 to 32 months after discharge,and 13 children(72.22%)had seizure termination in 5 days to 5 months(median 22.00,IQR 8.50-90.00)after the start of treatment,of whom 6 cases(46.15%)within 2 weeks,7 cases(53.85%)beyond 2 weeks,and 2 out of 13 cases(15.38%)had recurrence;13 cases reviewed EEG review during follow-up,of whom 5 cases(38.46%)were normal,3 cases(23.08%)still had hypsarrhythmia,and 5 cases(38.46%)had abnormal slow background or other forms of epileptic discharge waves.(3)Of these 22 children with IS,17 cases(77.27%)had epilepsyrelated gene mutation detected,5 cases(22.73%)had no epilepsy-related gene mutation.Of the 17 children with epilepsy-related gene mutations,12 cases(70.59%)inherited non-pathogenic mutations from their father or mother,5 cases(29.41%)were new and pathogenetic mutations,including: 2 cases had STXBP1 gene mutations,of whom 1 had STXBP1 deletion mutation,1 had STXBP1 splicing mutation,and 1 had SCN2 A missense mutation;1 had KCNQ3 missense mutation;1 had EEF1A2 missense mutation.(4)Of these 22 patients,5 patients had pathogenic gene mutations,including 4 females(80.00%),1 male(20.00%),17 cases had nonpathogenic gene mutations,including 10 females(58.82%)and 7 males(41.18%);compared with children with non-pathogenic gene mutations(n=2,11.76%),children with pathogenic gene mutations(n=3,60.00%)were more likely to have other forms of epileptic seizures before spasms;infants with pathogenic gene mutations(3 months)had earlier onset of spasms than those with non-pathogenic gene mutations(5 months).There was no significant difference in spasms types and EEG changes between these two groups.(5)Compared with 17 children(n=14,82.35%)with non-pathogenic gene mutations,5 children(n=5,100.00%)with pathogenic gene mutations preferred to use AED alone or in combination with other drugs,and they use more kinds of AEDs(median 3.00,IQR 1.50-3.00)than those with non-pathogenic gene mutations(median 2.00,IQR 1.50-3.00).3(75.00%)of the 5 cases with pathogenic gene mutations had seizure termination more than two weeks after the start of treatment(median 23 days),with no recurrence,EEG was reviewed in 2 cases,indicating spike-sharp wave and abnormal slow background.Of the 17 children with pathogenic gene mutations,10 case(71.43%)had spasms termination,of whom 6(60.00%)were within 2 weeks after treatment and 4(40.00%)were beyond 2 weeks(median 12.00,IQR 7.50-127.50).2 patients(20.00%)had spasms recurrence during follow-up.11 children with non-pathogenic gene mutations reviewed EEG,of whom 5(45.45%)were normal,3(27.27%)still had hypsarrhythmia,and 3(27.27%)showed other forms of epileptic discharge waves and abnormal slow background.Conclusion:(1)Of these 22 infants with unexplained infantile spasms,17 cases(77.27%)had epilepsy-related genes detected,and 5(29.41%)of them were pathogenic gene mutations,suggesting that genetic screening is recommended for children with unexplained IS.(2)Compared with children with non-pathogenic gene mutations,there are more girls in those children with pathogenic gene mutations,and they were more likely to have other forms of epileptic seizures before the onset of spasms,as well as have earlier IS onset,prefer AED alone or in combination with other medications,use more kinds of AEDs,experience longer time between the start of treatment and seizure termination,have less recurrence and present no hypsarrhythmia of EEG during follow-up,otherwise it still needs large sample studies.(3)The gene mutations of STXBP1,SCN2 A and EEF1A2 in this study are mostly consistent with those reported internationally,while KCNQ3 may be a new pathogenic mutation for IS,which expands the gene library. |
PDF Full Text Request