新生儿惊厥33例临床特征及高通量测序检测分析  

Clinical characteristics and next-generation sequencing analysis of 33 cases of neonatal seizures

作　　者：郑思敏 张永红[1] 赵冬莹[1] 谭金童 何振娟[1] 朱天闻[1] Zheng Simin;Zhang Yonghong;Zhao Dongying;Tan Jintong;He Zhenjuan;Zhu Tianwen(Department of Neonatal Medicine,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院新生儿科,200092

出　　处：《中华新生儿科杂志（中英文）》2020年第3期202-206,共5页Chinese Journal of Neonatology

摘　　要：目的探讨不明原因新生儿惊厥的临床特征及分子诊断结果。方法回顾性分析2016年1月至2018年12月上海交通大学附属新华医院新生儿科收治的临床诊断新生儿惊厥、因病因不明行高通量测序检测的新生儿,收集相关临床资料及高通量测序结果,并随访患儿的临床转归情况。结果共纳入33例,男18例,女15例。均以惊厥发作为首发症状,其中单一惊厥发作6例(18.2%),有其他伴随症状27例(81.8%),包括惊厥外神经系统症状18例(54.5%)、呼吸系统症状13例(39.4%)、代谢和内环境紊乱12例(36.4%)、喂养困难6例(18.2%)、多发畸形6例(18.2%)、心血管系统和血液系统异常各2例(6.1%)。26例行医学外显子测序(clinical exome sequencing,CES),7例行全外显子测序(whole exome sequencing,WES)。通过高通量测序明确诊断13例,阳性率39.4%;CES检测阳性率46.2%(12/26),WES检测阳性率14.3%(1/7)。分子诊断阳性的患儿中,5例为先天遗传代谢病,4例为原发性癫痫。共检出11个致病基因及染色体大片段缺失,其中9个变异未曾报道。结论不明原因新生儿惊厥无临床特异性表现,但以合并神经系统、呼吸系统、代谢和内分泌系统症状为主,通过高通量测序,本组病例中39.4%的患儿诊断为先天性遗传病,提示高通量测序对不明原因新生儿惊厥的早期诊断具有重要意义。Objective To study the clinical features and molecular diagnosis of neonatal seizures of unknown causes.Method Clinical data and test results of newborns who were admitted to the Neonatal Department of Xinhua Hospital from January 2016 to December 2018 and diagnosed with neonatal seizures of unknown causes and received next-generation sequencing were retrospectively collected.The clinical outcomes of these infants were also followed up.Result A total of 33 Chinese neonatal patients who met the criteria were included in the study,including 18 males and 15 females.Seizures were the onset symptoms of all neonatal patients,of which 6 cases(18.2%)without with no other neurological abnormalities or accompanied symptoms.Among the rest of 27 cases(81.8%),18 infants(54.5%)had other neurological manifestations,13 cases(39.4%)had abnormal respiratory system manifestations,12 cases(36.4%)had metabolic and internal environment disturbance,6 case(18.2%)had feeding difficulties,6 cases(18.2%)had multiple malformations,2 cases(6.1%)had abnormal cardiovascular system manifestations,and 2 cases(6.1%)had abnormal hematological system manifestations.According to the clinical characteristics of the infants,26 patients underwent clinical exome sequencing(CES)and the other 7 underwent whole exome sequencing(WES).The results of 13 infants(13/33,39.4%)turned out to be positive.Among the patients with positive results,CES provided higher molecular yields for 12 of 26 patients(46.2%)while WES did those for 1 of 7(14.3%).The diagnoses of patients with positive results included inborn error of metabolism in 5 cases and primary epilepsy in 4 cases.A total of 11 pathogenic genes and a large fragment deletion at the chromosome level were detected,9 of which were previously unreported.Conclusion Neonatal seizures of unknown causes has no specific clinical manifestation,majority of the patients are accompanied with other abnormalities,and 39.4%of the patients are diagnosed as genetic diseases by next-generation sequencing.The results suggest that

关 键 词：惊厥性发作 婴儿 新生 高通量核苷酸测序 表型 分析 

分 类 号：R722[医药卫生—儿科]