| Objective: To explore the clinical phenotype and genotype characteristics of children with SCN1 A gene-related febrile sensitive diseases,and to provide evidence for early identification of severe clinical phenotypes and clinical individualized diagnosis and treatment.Methods: We retrospectively analyzed the clinical data,auxiliary examination,gene results and antiepileptic drugs(AEDs)treatment of 38 patients with fever sensitivity and SCN1 A gene mutation positive who were admitted to the pediatric outpatient department and inpatient department of the First Affiliated Hospital of Guangxi Medical University from January 1,2016 to December 31,2020.According to the severity of clinical phenotypes,patients were divided into severe Dravet syndrome group(n=27)and mild non-Dravet syndrome group(n=11),The non DS group included generalized tonic clonic epilepsy,febrile convulsion(FS)and febrile convulsion plus(FS +).Statistical methods were used to compare the age of onset,the age of the convulsion onset less than 6 months,cluster seizure,presence of epileptic status,age without febrile seizure for the first time and duration of first seizure between the two groups.According to the missense mutation site of SCN1 A gene,the patients were divided into core coding region group and non core coding region group.according to the mutation types and mutation sites of SCN1 A gene,patients were divided into truncation mutation + core coding region of missense mutation group and non-core coding region of missense mutation group,and the clinical phenotypes of the two groups were compared.To analyze the relationship between clinical phenotype and genotype of SCN1 A gene-related febrile sensitive diseases.Results :(1)The onset age ranged from 2 to 48 months,with a median age of 5.5 months.(2)The first onset of febrile convulsion was 33 cases(33/38,86.84%).Among them,5 cases(5/32,15.63%)were induced seizures after vaccination.And 6 cases(5/38,13.16%)without febrile convulsion.(3)Eight types of seizures were observed,including: generalized tonic-clonic seizure,focal seizures,absence seizure,atypical absence seizures,myoclonic seizures,atonic seizure,tonic-closure seizures,spastic seizure.22cases(22/38,57.89%)had status epilepticus(SE),and 26 cases(26/38,68.42%)had cluster seizures.(4)Family history: 7 cases(7/38,18.42%)first-degree relatives had a family history of febrile seizures,2(2/38,5.26%)first-degree relatives had a family history of epilepsy,and 1(1/38,2.63%)mother had mental retardation.(5)Developmental status: At the end of the follow-up,all the children were assessed for intelligence development,11 cases were evaluated by Gesell scale:5 cases had normal mental development,5 cases of developmental delay and 1case of general retardation.The 27 patients were evaluated by Wechsler scales: 5cases(13.16%)had normal intelligence,3 cases had low intelligence,3 cases had mild mental retardation,8 cases had moderate mental retardation,6 cases had severe mental retardation and 2 cases had extremely severe mental retardation.(6)EEG: 7 cases(7/38,18.42%)had normal EEG monitoring during follow-up.31 cases(31/38,81.58%)of EEG showed focal or multiple or multiple spike wave,spike slow wave,sharp wave,sharp slow wave,sharp slow wave,and sharp slow wave.(7)Among the 38 children,28 cases(28/38,73.68%)had new SCN1 A mutations,and 10 cases(10/38,26.32%)had genetic mutations,of which 6 cases were from the mother and 4 cases were from the father.There were 17 cases(17/38,44.74%)of missense mutation,21 cases(21/38,55.26%)of truncation mutation.(8)Clinical phenotype: Of the 38 children,27(27/38,71.05%)were diagnosed with Dravet syndrome(DS),1(2.63%)was Epilepsy with generalized tonic-clonic seizures,2(5.26%)with febrile seizure,and 8(21.05%)with febrile seizure plus(FS+).(9)Therapeutic effect: In 27 patients with Dravet syndrome,2 patients(7.4%)had controlled seizure,14 patients(51.85%)had a reduction of more than 50%,10 patients(10/27,37.04%)had a reduction of less than 50%,and 1patient(3.7%)had no reduction.In non-Dravet patients,3 patient(27.27%)had seizure control,7 patient(63.64%)had seizure reduction of more than 50%,and1 patient(10%)had seizure reduction of less than 50%.(10)Effect of sodium channel blockers antiepileptic drugs: before the diagnosis of DS,children in this group had used sodium channel blocker antiepileptic drugs,including 4 cases had used carbamazepine,3 cases had used lamotrigine,5 cases had used oxcarbazepine,75%(9/12)were ineffective,and25%(3/12)had aggravated seizures.(11)There were no statistically significant differences between the Dravet syndrome group and the non-Dravet syndrome group in cluster seizures,but there were statistically significant differences between the two groups in the age of the convulsion onset less than 6 months,the duration of the first seizure of more than 5 minutes,the first seizure without heat convulsion before the age of2 years and epileptic status(P < 0.05).(12)The therapeutic effect of the DS group was compared with that of the non-DS group.The curative effect of the non-DS group was better,and the difference between the two groups was statistically significant(P < 0.05).(13)There were statistically significant differences in clinical phenotypes between truncation mutation + core coding region of missense mutation group and non-core coding region of missense mutation group(P < 0.05).Conclusion:(1)The phenotype of SCN1 A gene-associated febrile sensitive disorders is extensive,ranging from mild febrile seizure to severe Dravet syndrome.The age of onset of SCN1 A gene mutation is less than 6 months,the duration of the first seizure is more than 5 minutes,the first non-fever convulsion occurs before the age of 2 years,the occurrence of epileptic status indicated the high possibility of Dravet syndrome.(2)The truncation mutation or missense mutation located in the core coding region of the SCN1 A gene mutation indicated the high possibility of Dravet syndrome.(3)Antiepileptic drugs(AEDs)with sodium channel blockers should be avoided in children with SCN1 A gene-related diseases. |
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