Relationship between mutation characteristics of SCN1A gene in Dravet syndrome and its clinical phenotype and drug efficacy
10.3760/cma.j.issn.2095-428X.2019.09.011
- VernacularTitle: Dravet综合征患儿SCN1A基因突变特点与其临床表型的相关性及药物疗效
- Author:
Cui WANG
1
;
Tianming JIA
;
Xiaoli ZHANG
;
Man ZHAO
;
Qiliang GUO
;
Yangyang QIN
;
Chenge YAN
Author Information
1. Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Publication Type:Journal Article
- Keywords:
Dravet syndrome;
SCN1A gene;
Mutation;
Clinical phenotype
- From:
Chinese Journal of Applied Clinical Pediatrics
2019;34(9):684-688
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the relationship between different mutation characteristics and clinical phenotype of children with Dravet syndrome (DS) with SCN1A gene mutation, and to summarize the drug efficacy.
Methods:The clinical data of children diagnosed as DS from the Department of Pediatrics Neurology, the Third Affi-liated Hospital of Zhengzhou University from January 2014 to May 2018 were collected.The peripheral blood DNA of the children was detected by adopting next generation sequencing for epilepsy-related gene-panel, while the parents′ were screened by using Sanger sequencing for family verification.Multiple ligation-dependent probe amplification technology was used to detect large fragment variation of SCN1A gene if the mutations of the children were negative.The Gesell scale and cavity Wechsler intelligence scale for children(C-WISC) were used to evaluate the intelligence of children.
Results:A total of 50 cases of DS were collected, 38 cases of them were positive for SCN1A mutation, and the mutation rate was 76.0%(38/50 cases), of which, the missense mutation[50.0%(19/38 cases)] and frameshift mutation[28.9%(11/38 cases)] were dominant.The average onset age of 50 patients was 6 months, of which onset of seizures was triggered by fever(temperature>37.5 ℃) in 68.0%(34/50 cases)of children, the history of seizures in hot baths was found in 60.0%(30/50 cases) of children, status epilepticus was found in 74.0%(37/50 cases), cluster-like episodes was found in 80.0%(40/50 cases), ≥2 seizure types was found in 92.0%(46/50 cases). Mental retarda-tion was found in most of the children, of which 30.0% (15/50 cases) were mild mental retardation, 38.0% (19/50 cases) were moderate mental retardation, 14.0% (7/50 cases)were severe intelligence retardation.Interictal abnormalities of electroencephalogram(EEG) before 1 year old was found in 24.0%(12/50 cases), and the average age of EEG abnormalities was 30.12 months old; the top three drug efficacy rates were 70.0% (28/40 cases) of Topiramate, 48.0% (24/50 cases) of Sodium Valproate, 45.7% (16/35 cases) Clonazepam or Clobazam.The time of onset of myoclonus and atypical absence of the truncation mutation group was earlier than that of the missense mutation group(14.75 months vs.21.20 months; 16.82 months vs.26.00 months), and the difference was statistically significant(P<0.05). The proportion of clustered episodes in the truncation mutation group was higher than that in the missense mutation group [94.7%(18/19 cases)vs.63.2%(12/19 cases)], and the difference was statistically significant (P<0.05). There was no significant correlation between the SCN1A gene mutation (type and position) and age of onset, type of seizure, proportion of convulsion persistence, the mental development or abnormal proportion of EEG and seizure frequency before 1 year old(all P>0.05).
Conclusions:The SCN1A gene mutation rate is high in children with DS, and the SCN1A gene mutation characteristics has a certain correlation with DS clinical phenotype.Topiramate is the most effective drug among children with DS.
