摘要
目的探讨过度惊吓反应症的临床特征及基因变异特点。方法回顾性分析1例确诊为过度惊吓反应症患儿的临床资料及基因检测结果,并通过文献检索总结分析中国过度惊吓反应症患儿的临床及基因特征。结果患儿,男,年龄5个月10 d。出生后18 d起在突发外界声音刺激时出现惊跳,继而躯干及四肢出现僵直,近2个月症状加重伴窒息。起病后运动发育落后。视频EEG及头颅MRI均正常。基因变异分析提示GLRA1基因复合杂合突变,第9号外显子c.1246 G>A及第4号外显子c.370 C>T杂合错义突变。诊断过度惊吓反应症后给予氯硝西泮口服,症状明显改善,发育恢复正常。同时进行文献检索共有12篇报道22例中国人群过度惊吓反应症的病例,加上本例患儿共23例进行总结。其中男性多于女性,男女比为2.3∶1。95.7%患儿为婴儿期起病,其中73.9%为新生儿期发病。婴儿期主要临床症状包括过度惊吓反应(100%)、全身僵硬(87.0%)、窒息(34.8%),11例患儿年长后出现刺激后摔倒表现,上述症状均可由不可预料的外界刺激诱发。部分患儿可伴有脐疝(21.7%)及腹股沟疝(8.7%),1例同时伴婴儿痉挛症。92.9%患儿点鼻反射阳性。在确诊前,9例(39.1%)患儿曾诊断为癫痫,3例为新生儿惊厥,1例为发作性非运动诱发的运动障碍。除1例合并癫痫外,另有10例曾给予抗癫痫药物治疗,疗效均不佳。8例有阳性家族史。8例发育正常,4例运动发育落后,11例患儿年长后表现为宽基底样步态行走。发作期EEG除夹杂大量肌电伪差外,均未见痫样放电。20例患儿进行基因检测,16例为GLRA1基因突变,其中6例为常染色体显性遗传,10例为常染色体隐性遗传,3例携带GLRB基因复合杂合突变,1例全外显子测序结果为阴性。1例患儿未经治疗,症状自行好转。21例经氯硝西泮治疗后症状显著好转,仅1例无效。结论过度惊吓反应症具有典型的临床特点,但容易误诊,视频EEG联合同步EMG及基因检测有助于早期诊断。氯硝西泮有较好的疗效,早期诊治可提高患儿预后。
Objective To explore the clinical characteristics and genetic mutations of hyperekplexia.MethodsA retrospective analysis was performed for the clinical and genetic data of one patient with hyperekplexia.And the clinical and genetic characteristics of patients with hyperekplexia in Chinese population were analyzed by literature review.Results A 5-months-old boy showed exaggerated startle reflexes and generalized stiffness which were easily provoked by external sudden and unexpected stimuli since 18 days after birth.These symptoms worsened in recent 2 months and asphyxia occurred.After the onset of disease,this boy had motor developmental delay.There were no obvious abnormal findings in EEG and brain MRI.The patient was revealed to have compound heterozygous mutations in GLRA1 gene,c.1246 G>A and c.370 C>T.Clonazepam was given after the diagnosis of hyperekplexia established.The symptoms of both startle reflexes and generalized stiffness were controlled with clonazepam.And his motor development was gradually normal.Literature retrieval obtained 12 reports with 22 cases of hyperekplexia.There were more males than females(male-female ratio was 2.3∶1).The onset age of 95.7%of the patients was in infancy and 73.9%in neonatal period.The main clinical symptoms in infancy included exaggerated startle reflexes(100%),generalized stiffness(87.0%),and asphyxia(34.8%).Eleven cases showed fall when they grew up.And the above symptoms were easily provoked by external stimuli.Umbilical hernia(21.7%)and inguinal hernia(8.7%)may occur in those patients.One case was accompanied with infantile spasms.92.9%of all cases had the positive nose-tapping reflex.Before the diagnosis of hyperekplexia,9 children(39.1%)had diagnosed with epilepsy,3 with neonatal convulsions,and 1 with paroxysmal non-kinesigenic dyskinesia.Except for one case with epilepsy,another 10 cases had been treated with antiepileptic drugs,but had no efficacy.Eight patients had positive family history.Eight children had normal mental and motor development,but four showed motor developmental delay.Eleven cases showed a cautious gait with a wide stride.Ictal EEG exhibited artifacts without any epileptiform discharge.Genetic analysis was performed in 20 children.GLRA1 gene mutation was found in 16 cases.Among them autosomal dominant inheritance was seen in 6 cases and autosomal recessive inheritance in 10.Three cases carried complex heterozygous mutation ofGLRBgene,and 1 case had negative result.The symptoms improved spontaneously without any treatment in 1 case.Except for one case,the symptoms of another 21 patients were significantly improved after treatment with clonazepam.Conclusions The patient presented typical clinical manifestations of hyperekplexia.However,it is easy to be misdiagnosed.Video EEG combined with synchronous electromyography and genetic analysis are helpful for early diagnosis.The patients have a good response to clonazepam.Early diagnosis and treatment can improve the prognosis.
作者
陈嘉蕾
徐洋
胡文广
刘平
邓佳
王燕娟
蓝明平
李思秀
CHEN Jia-lei;XU Yang;HU Wen-guang(Department of Pediatric Neurology,Chengdu Women’s and Children’s Central Hospital,School of Medicine,University of Electronic Science and Technology of China,Chengdu 611731,China)
出处
《临床神经病学杂志》
CAS
2022年第2期131-136,共6页
Journal of Clinical Neurology
