摘要
目的 探讨DEPDC5基因变异导致家族性局灶性癫痫伴可变灶(familial focal epilepsy with variable focal type,FFEVF)的临床特征、遗传学特征及治疗情况,提高对FFEVF的认识.方法 对中国人民解放军联合后勤保障部队第980医院新生儿科诊断为FFEVF患儿的临床特征、遗传变异类型、家系发病情况和治疗状况进行回顾性分析.以"家族性局灶性癫痫伴可变灶""DEPDC5 基因"和"familial focal epilepsy with variable focal type""DEPDC5 gene"为主题词,对中国知网、万方数据、中华医学期刊全文数据库、PubMed、Web of Science、Embase及Cochrane Library数据库收录的文献进行检索,检索时间自建库至2023年12月1日,总结FFEVF患儿的DEPDC5基因变异类型及治疗情况.结果 本例患儿女,生后第5天出现抽搐,表现为四肢不自主抖动,肌张力高,同时伴有呼吸急促、抽泣样呼吸、吸气性三凹征、吸气性喉鸣音、脉搏氧饱和度下降等表现,常规抗癫痫药物控制不佳.其母有难治性癫痫病史.对患儿及其父母行全外显子测序,患儿及其母亲DEPDC5基因存在c.1067G＞A(p.Arg356Gln)错义变异,父亲为野生型.其母家系相关成员(外祖父、外祖母,2个舅舅)进行该变异位点验证,结果显示患儿外祖父及1个舅舅存在相同位点变异.患儿生后39 d给予氨己烯酸治疗,现1.5岁,未再有癫痫发作,因经济原因其母未给予氨己烯酸治疗,目前常规抗癫痫药物治疗,每周发作3～5次.文献复习共总结19个家系、71名成员,发现19个变异位点,给予常规抗癫痫治疗后,13个家系描述了预后,6个家系预后良好,6个家系出现伴随症状,1个家系发展为难治性癫痫.结论 FFEVF多数由DEPDC5基因变异导致,本例患儿DEPDC5基因c.1067G＞A(p.Arg356Gln)变异为新发现的变异,国内外尚未报道;DEPDC5基因变异导致FFEVF引起的难治性局灶性癫痫患儿可尝试应用氨己烯酸治疗.
Abstract
Objective To study the clinical characteristics,genetic features and treatment of familial focal epilepsy with variable focal type(FFEVF)caused by DEPDC5 gene mutation.Methods The clinical data of a neonate diagnosed of FFEVF in our hospital were reviewed.Using"familial focal epilepsy with variable focal type"and"DEPDC5 gene"as keywords,relevant literature were searched in multiple medical databases from inception to December 1,2023.The genetic profiles of DEPDC5 gene mutations and treatment of FFEVF cases were summarized.Results The neonate(female)in our hospital developed convulsions of involuntary limb tremors and elevated muscle tone on d5 after birth.She also had shortness of breath,breath-holding spells,intercostal retractions,laryngeal stridor and decreased pulse oxygen saturation.Conventional antiepileptic drugs(AEDs)failed to achieve effective control.Her mother had a history of refractory epilepsy.Whole exome sequencing(WES)revealed a missense mutation of c.1067G＞A(p.Arg356Gln)on DEPDC5 gene in both the neonate and her mother,while the father had wild type.Further verification of the mutation in maternal family members(maternal grandfather,grandmother and two uncles)showed that the maternal grandfather and one uncle also carried the same variant.The patient was treated with vigabatrin at 39 d after birth and now she was 1.5-years-old,seizure-free.Due to financial constraints,her mother did not receive vigabatrin treatment and continued with conventional AEDs,experiencing 3-5 episodes of seizures per week.The literature review identified 19 families with 71 members and 19 loci.With conventional AEDs treatment,the prognosis was described in 13 families.6 had favorable prognosis,6 developed concomitant symptoms and one developed refactory epilepsy.Conclusions FFEVF is mostly caused by DEPDC5 gene mutations.The c.1067G＞A(p.Arg356Gln)variant in our case is a novel mutation,which has not been reported.Vigabatrin may be considered for FFEVF caused by DEPDC5 gene mutations.
维普
万方数据