DSG2/PKP2/DSP基因变异相关儿童致心律失常型右室心肌病的临床表型及基因型特点分析  

Clinical phenotype and genotype characteristics of arrhythmogenic right ventricular cardiomyopathy in children with DSG2/PKP2/DSP variants

作　　者：那嘉[1] 袁越[1] 李奇蕊 陈希[1] 甄珍[1] 田芝瑜 高路[1] Na Jia;Yuan Yue;Li Qirui;Chen Xi;Zhen Zhen;Tian Zhiyu;Gao Lu(Department of Cardiology,Beijing Children's Hospital Capital Medical University,National Children's Medical Center,Beijing 100045,China)

机构地区：[1]国家儿童医学中心,首都医科大学附属北京儿童医院心脏内科,100045

出　　处：《中国小儿急救医学》2024年第4期250-255,共6页Chinese Pediatric Emergency Medicine

摘　　要：目的总结DSG2/PKP2/DSP基因变异相关儿童致心律失常型右室心肌病(ARVC)的临床表型及基因型特点,为儿科精准化诊治ARVC提供依据。方法回顾性分析2018年1月至2023年6月在首都医科大学附属北京儿童医院诊治的7例DSG2/PKP2/DSP基因变异致ARVC患儿的临床资料,基因检测采用靶向高通量二代测序法,并通过Sanger进行家系成员验证。结果7例(男3例、女4例)患儿入院年龄中位数为11.8岁。7例患儿心电图及24 h动态心电图均记录到室性心律失常。7例患儿超声心动图提示右心室不同程度扩大,2例合并左心室扩大。心脏磁共振成像显示2例患儿右室壁运动幅度减低,4例患儿双心室室壁运动异常;3例患儿双心室心肌可见延迟强化信号,2例左心室心肌可见延迟强化信号。4例患儿存在DSG2基因变异,其中3例为复合杂合变异,1例为纯合变异;2例患儿分别存在PKP2和DSP基因杂合变异;1例患儿同时存在PKP2和DSP基因杂合变异。7例患儿共检测到9个基因变异位点,其中5个为未报道的新变异。6例经家系验证,5例患儿为家族遗传性变异,1例为自发变异。7例患儿均给予β受体阻滞剂和(或)胺碘酮口服抗心律失常治疗,6例给予抗心力衰竭治疗。随访3~50个月,1例死亡,1例因严重全心功能衰竭行心脏移植术。结论儿童ARVC临床表现差异大,左心室受累患儿预后较差;基因检测有助于早期诊断和风险评估;尽早干预及药物治疗可延缓部分患儿的病情进展;5个新变异丰富了ARVC的基因突变谱。Objective To summarize the clinical phenotype and genotype characteristics of arrhythmogenic right ventricular cardiomyopathy(ARVC)in children associated with DSG2/PKP2/DSP gene mutations,providing information for precise diagnosis and treatment for ARVC in children.Methods A retrospective analysis was conducted on the clinical data of seven patients with ARVC caused by DSG2/PKP2/DSP gene mutations who were diagnosed and treated at Beijing Children's Hospital from January 2018 to June 2023.Gene testing was performed using targeted high-throughput second-generation sequencing,and family member validation was conducted using Sanger method.Results The median admission age of seven patients(three males and four females)was 11.8 years old.Ventricular arrhythmia was recorded on the electrocardiogram and Holter monitor of seven cases.Ultrasonic cardiogram showed varying degrees of right ventricular enlargement of seven cases,while two cases also had left ventricular enlargement.Cardiac magnetic resonance imaging showed a decrease in the amplitude of right ventricular motion in two cases,and abnormal dual ventricular motion in four cases.Delayed enhancement signals were observed in the biventricular myocardium in three cases,and in the left ventricular myocardium in two cases.Four patients had DSG2 gene mutations,of which three patients were compound heterozygous and one patient was homozygous.Two patients had heterozygous mutations in PKP2 and DSP genes,respectively.One patient had both PKP2 and DSP gene heterozygous mutations.A total of nine gene mutations were detected in seven patients,of which five patients had unreported new mutations.After family verification,five of the six cases had familial genetic mutations and one had spontaneous mutations.All seven patients were givenβreceptor blocker and/or amiodarone for antiarrhythmic treatment,and anti-heart failure treatment was also administered.Follow up during 3 to 50 months,one patient died,and one patient underwent heart transplantation due to severe heart failure

关 键 词：致心律失常型心肌病 儿童 基因 诊断 预后 随访 

分 类 号：R725.4[医药卫生—儿科]