小婴儿期起病的儿童交替性偏瘫5例临床表型与基因型分析  

Analysis of clinical phenotype and genotype of alternating hemiplegia of childhood in 5 children with onset in early infancy

作　　者：周娜 武运红 韩虹[2] 王文徽 郭佳佳 郭瑾 ZHOU Na;WU Yunhong;HAN Hong;WANG Wenhui;GUO Jiajia;GUO Jin(Department of Pediatric Medicine,Shanxi Medical University,Taiyuan 030001,China;Department of Neurology,Children′s Hospital Affiliated to Shanxi Medical University)

机构地区：[1]山西医科大学儿科医学系,太原030001 [2]山西医科大学附属儿童医院神经内科

出　　处：《山西医科大学学报》2024年第10期1352-1357,共6页Journal of Shanxi Medical University

摘　　要：目的 总结小婴儿期起病的儿童交替性偏瘫(alternating hemiplegia of childhood, AHC)的临床表型及基因型特点。方法 回顾性收集2021年4月至2023年3月在山西省儿童医院神经内科门诊及住院病房就诊的5例小婴儿期起病的AHC患儿的临床资料。采集患儿及其父母外周血DNA,采用全外显子组测序技术对其行基因检测,并对其临床表型及基因型进行分析。结果 5例患儿中男2例,女3例,起病年龄最小为17 d,最大为6月龄,平均起病年龄为3月龄。3例患儿起病前有明显诱因。5例患儿均有眼球运动异常表现,其首次偏瘫发作年龄为3~18月;偏瘫发作频率最小为5~9 d发作1次,1例患儿目前仅发现1次偏瘫发作;5例患儿中偏瘫持续时间最短为20~30 min,最长为2~3 d。服用氟桂利嗪后患儿的发作频率均有不同程度的降低,但每次发作持续的时间无明显变化。通过基因检测共发现3种突变类型:2种为杂合错义突变,分别为D801N(c.2401G>A)和L798P(c.2393T>C);1种为缺失突变,2381_2383del(p.Thr794del),其中携带D801N基因突变者3例,其余各1例。其中突变2381_2383del(p.Thr794del)尚未在ClinVar数据库收录。结论 对于起病年龄较早,以眼球运动异常或肌张力障碍等为首发症状,发作性症状在睡眠期和觉醒后缓解或消失,头颅MRI和EEG均正常时,需警惕交替性偏瘫可能。本研究尚未发现小婴儿期起病的AHC患儿的基因型特异性,可能与3种变异均位于α3亚基的M6跨膜区域,对Na+/K+-ATP酶离子转运的影响水平相似有关。Objective To summarize the characteristics of clinical phenotype and genotype in alternating hemiplegia(AHC)children with onset in early infancy.Methods The clinical data of 5 infants with AHC in the outpatient and inpatient wards of department of neurology in Shanxi Children′s Hospital from April 2021 to March 2023 were analyzed retrospectively.The peripheral blood DNA of children and their parents were collected for the gene analysis by whole exon sequencing,and their clinical phenotypes and genotypes were analyzed.Results Of the 5 cases,there were 2 males and 3 females.The minimum age of onset was 17 d,the maximum was 6 months,and the average age of onset was 3 months.Three cases had obvious causative factors before onset.All the 5 children had abnormal eye movement,the age of the first onset of hemiplegia was from 3 months to 18 months,and the lowest frequency of hemiplegia was once every 5-9 d.The shortest duration of hemiplegia was 20-30 min and the longest was 2-3 d.One case had hemiplegia only once.After taking Flunarizine,the seizure frequency decreased in varying degrees,but the duration of each attack had no significant change.Three types of mutations were found by gene detection,including three cases of D801N(c.2401G>A),one case of L798P(c.2393T>C),and one case of 2381_2383del(p.Thr794del).The mutant 2381_2383del(p.Thr794del)has not been included in the ClinVar database.Conclusion The alternating hemiplegia should be alerted when the age of onset is early,the first symptom is abnor‐mal eye movement or dystonia,the paroxysmal symptoms are relieved or disappear during sleep and after awakening,and the cranial MRI and EEG are normal.The genotype specificity has not been found in AHC children with onset in early infancy,which may be related to the similarity of effect of the three variants in the M6 transmembrane region of theα3 subunit on Na+/K+‐ATPase ion transport.

关 键 词：儿童交替性偏瘫 ATP1A3基因 临床表型 基因型 癫痫 眼球运动异常 氟桂利嗪 

分 类 号：R725[医药卫生—儿科]