摘要
目的探讨RARS2基因变异的临床特点。方法回顾分析一家系2例RARS2基因变异患儿的临床资料,并复习相关文献。结果2例患儿为姐妹,均于4月龄起病,表现为喂养困难、顽固性局灶性癫痫发作、四肢肌张力减低、小头畸形,血乳酸一过性升高;头颅磁共振示双侧大脑半球萎缩,右侧颅板下出血,右侧基底节区异常信号。先证者检测到RARS2基因复合杂合变异,NM_020320 c.1157G>T(p.R 386L),NM_020320 c.1210A>G(p.M 404V)。先证者姐姐首次基因检测无发现,再次分析发现RARS2基因同样变异,并于1岁4月龄死亡。检索到相关文献19篇,包括本家系2例共37例患儿。其中男37.2%、女62.8%,大多在6月龄内起病;临床表现有癫痫发作,精神运动发育停滞或倒退,喂养困难,肌张力减低,小头畸形;大部分患儿血、脑脊液乳酸增高及脑桥小脑发育不良。共发现RARS 2基因33个变异位点。结论RARS2基因变异的临床表现有顽固性癫痫发作、喂养困难、精神运动发育迟滞或倒退、小头畸形、肌张力减低,部分患儿无桥脑小脑发育不良,预后差。
Objective To explore the clinical characteristics of children with RARS2 gene variation and to review the literature.Methods Clinical data of two siblings with RARS2 mutation were retrospectively analyzed,and the data of 35 children with RARS2 gene variation in the literature were reviewed.Results Both case one and case two were female with the onset of the disease at the age of 4 months,presenting with feeding difficulties,intractable focal seizures,hypotonia,microcephaly,and transient or continuous increased actic acid.Brain MRI in case one showed progressive cerebral atrophy,right subcranial plate hemorrhage,and abnormal signals in the right basal ganglia.She died at the age of 1 year and 4 months.Brain MRI in case 2 showed abnormal signals in bilateral temporal region and progressive cerebral atrophy.Gene detection identified compound heterogeous mutations c.1157G>T(p.R 386L)and c.1210A>G(p.M404V)in RARS2 gene.A total of 37 cases of children,37.2%male and 62.8%female,were found in the literature.Most of them started the disease within 6 months,with clinical manifestations including epileptic seizure,psychomotor development stagnation or regression,feeding difficulties,decreased muscle tone and microcephaly.Most of the children with increased blood,cerebrospinal fluid lactic acid and pontocerebellar dysplasia.A total of 33 RARS2 gene mutation sites were found.Conclusion Seizures,feeding difficulties,psychomotor retardation or regression,microcephaly,dystonia,increased lactic acid and pontocerebellar hypoplasia,which mayindicate the possibility of RARS2 gene variants,and genetic testing can be diagnostic.Prognosis of this diorder is poor.
作者
张桐
汤继宏
王曼丽
黄静
张兵兵
ZHANG Tong;TANG Jihong;WANG Manli;HUANG Jing;ZHANG Bingbing(Department of Neurology,Children's Hospital of Soochow University,Suzhou 215003,Jiangsu,China;Xuzhou Children's Hospital,Xuzhou 221006,Jiangsu,China)
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2021年第8期583-587,共5页
Journal of Clinical Pediatrics
基金
苏州市科技计划(民生科技)项目(No.SS201866)
江苏省卫生健康委科研课题面上项目(No.H2018010)。