过度惊吓反应症临床及遗传学特征（附６例报告）

目的　分析6例过度惊吓反应症患儿的临床及遗传学特征。 方法　对2011年6月至2018年5月于北京大学第一医院诊断的6例过度惊吓反应症患儿的临床表现、诊治过程、脑电图（EEG）及神经影像学、遗传学结果等进行分析。 结果　6例中男5例、女1例。6例均为新生儿早期起病，均可因不经意的听觉或触觉刺激诱发过度惊跳反应和全身僵硬症状，3例曾出现短暂窒息发作，1例曾惊吓后摔倒致外伤。6例点鼻反射均阳性，4例合并疝。EEG示1例正常，5例为不典型放电或一过性异常。4例曾行头颅磁共振检查未见明显异常。经遗传学分析，6例中3例携带GLRA1基因杂合突变，2例携带GLRB基因复合杂合突变，1例经全外显子测序未发现基因突变。6例给予氯硝西泮治疗， 1例全身僵硬及过度惊吓反应均基本消失， 5例全身僵硬症状消失、偶有惊跳反应。6例智力发育均正常，2例存在宽基底步态状行走姿势。1例有相同症状而窒息死亡的明确家族史。 结论　过度惊吓反应症具有典型临床表现，点鼻反射阳性，可行基因诊断确诊。该病对氯硝西泮有良好的治疗反应。早期经临床诊断及基因确诊，及时、恰当治疗，对于改善预后至关重要。

Clinical and genetic characteristics hyperekplexia:A report of 6 cases

Objective To analyze the clinical and genetic characteristics of 6 patients with hyperekplexia.Methods Six patients were diagnosed with hyperekplexia in Peking University First Hospital between June 2011 to May 2018.The clinical presentations,course of treatment,electroencephalogram(EEG),cranial magnetic resonance imaging(MRI)and genetic results were analyzed.Results Of the 6 patients,5 were male,and one was female.All the patients presented exaggerated startle reflexes and generalized stiffness in response to unexpected auditory or tactile stimuli in the early neonatal period.Three patients had a transient asphyxia attack,and one had a traumatic fall after exaggerated startle.All the patients showed positive nose-tapping reflex,and four presented inguinal and/or umbilical hernias.EEG showed one was normal and there were atypical discharges or transient abnormality in 5.No obvious abnormalities were found in 4 patients who had undergone cranial MRI.Genetic analysis was performed in all 6 patients:three had heterozygous mutation of GLRA1 gene,two had complex heterozygous mutation of GLRB gene,and one had no gene mutation by whole exon sequencing.All the patients received the treatment of clonazepam.The symptoms of hyperekplexia were completely controlled in one,and only occasional exaggerated startle reflexes existed in 5.All had normal intellectual development,and two patients walked with a similar gait of wide base.One had a clear family history of asphyxia death with the same clinical symptoms.Conclusion All patients with hyperekplexia have typical clinical manifestations and positive nosetapping reflex.The diagnosis can be made through genetic diagnosis.All the patients have a good response to clonazepam.After early diagnosis through clinical diagnosis and genetic analysis,timely and appropriate treatment are crucial for improving the prognosis of this disease.