摘要
Background:West syndrome is a devastating disorder characterized by a triad of epileptic spasms,abnormal electroencephalography(EEG),and developmental arrest or psychomotor delay.In addition to early diagnosis,knowing the etiology of the condition is also important for its treatment.Among various etiologies,the genetic factors,especially mutations of ion channel genes,are very common and strongly linked to West syndrome.Case presentation:A boy who had epileptic spasms from the age of 4 months was diagnosed with West syndrome based on the clinical manifestation and EEG results in Shenzhen Children's Hospital in June 2019.Trios whole-exome sequencing(WES)test and protein structural model prediction were performed.We also reviewed the clinical and genetic features of this syndrome and the mechanisms of action of topiramate(TPM)by literature search in databases of Online Mendelian Inheritance in Man,Clinical Genome Resource,PubMed,Chinese National Knowledge Infrastructure and Wanfang database using keywords"KCNA2""West syndrome"and"Topiramate"by December 2020.The relationship between the effect of TPM and the pathogenesis of the KCNA2 variant was also assessed.The WES test revealed c.244C>T/p.Arg82Cys varaint of KCNA2(NM_004974.3)in this patient,and Sanger sequencing identified this was a de novo mutation.As far as we know,this is the first report of the C.244C>T/p.Arg82Cys variant in KCNA2,which was likely a pathogenic mutation.The seizures were successfully controlled for 10 months by TPM after failure of sodium valproate,large doses of vitamin B6,and adrenocorticotropic hormone.We speculate that the therapeutic effect of TPM in this patient is partially due to the inhibition of carbonic anhydrase.Conclusions:Mutations in the KCNA2 gene should be considered for patients with West syndrome.The TPM treatment is probably effective for KCNA2-associated disorders.
基金
This study was sponsored by the Sanming Project of Medicine in Shenzhen(SZSM 201812005)
Shenzhen Key Medical Discipline Construction Fund(SZXK033)
Epilepsy Research Fund of China Association Against Epilepsy(CU-C-2021-02)
Support Project for Clinical Research of Young and Middle-aged Doctors in South of the Ten Ridges Neurology(Z20210308).
