探讨先天性长QT综合征(LQTS)患儿的临床特征。

选择2021年7月于成都市妇女儿童中心医院诊治的1例2型LQTS(LQT2)患儿(先证者，男性，10岁)为研究对象。收集先证者临床病例资料及8名家系成员(母亲、父亲、胞弟、外公、外婆、爷爷、奶奶、舅舅)相关资料，绘制家系系谱图进行家系LQTS遗传学调查；对先证者及其父、母进行全外显子组测序(WES)及Sanger法测序验证，筛选出基因突变位点；对部分家系成员针对筛选出的突变位点进行Sanger法测序验证。结合先证者及其家系成员的临床病例资料及基因突变情况，对先天性LQTS的诊断及治疗进行分析。本研究通过成都市妇女儿童中心医院医学伦理委员会批准[审批文号：伦审2021(118)]，并取得患儿及监护人知情同意。

①先证者(男性，10岁)与母亲(31岁)均有反复晕厥病史，心电图结果均显示校正QT间期(QTc)>500 ms、T波存在切迹或双峰改变；先证者外公49岁时因"肝癌"去世，无明确晕厥病史，无心电图记录；家系成员中，除先证者母亲外，均无晕厥病史，心电图均显示QTc正常。②WES结果显示，先证者及母亲均为KCNH2基因c.94G>A(p.A32T)杂合突变、错义突变，先证者基因突变来自母亲；家系验证显示，先证者胞弟、父亲、舅舅及外婆该位点均无变异。③先证者与母亲均被确诊为LQT2亚型患者。对先证者采取盐酸普萘洛尔口服终身治疗措施，母亲采取盐酸普萘洛尔口服联合盐酸美西律口服终身治疗措施后，截至发稿对先证者及母亲均已经治疗及随访3^＋年，均无晕厥及心脏事件发生，复查心电图结果显示先证者QTc缩短、母亲QTc恢复至正常。

家系调查可及时发现家系中先天性LQTS患者。临床应重视晕厥患者心电图检查并正确测量QTc，避免LQTS患者被临床漏诊。β受体阻滞剂对先天性LQT2亚型患者治疗有效。

To explore the clinical characteristics of congenital long QT syndrome (LQTS) in children.

A 10-year-old male child (proband) diagnosed with type 2 LQTS (LQT2) at Chengdu Women′s and Children′s Central Hospital in July 2021 was enrolled. Clinical data from the proband and his 8 family members (mother, father, younger brother, maternal grandfather, maternal grandmother, paternal grandfather, paternal grandmother, maternal uncle) were collected. A pedigree map for LQTS genetic investigation of families of proband was constructed. Whole exome sequencing (WES) followed by Sanger sequencing validation were performed on the proband and parents to identify pathogenic variants. Sanger sequencing of the identified variant was conducted in selected family members. Based on the clinical data and genetic findings of the proband and his family members, the diagnosis and management of congenital LQTS were analyzed. This study was approved by the Medical Ethics Committee of Chengdu Women′s and Children′s Central Hospital [Approval No. Lun Shen 2021 (118)], and informed consent form was obtained from the child′s guardian.

① Both the proband (male, 10 years old) and the mother (31 years old) had a history of recurrent syncope, their electrocardiogram results showed a corrected QT interval (QTc) >500 ms and notched or biphasic T-waves. The proband′s maternal grandfather died of liver cancer at the age of 49, with no documented history of syncope or available electrocardiogram records. Other family members, except the proband′s mother, had no history of syncope, and their electrocardiogram results revealed normal QTc. ② WES revealed a heterozygous missense mutation of KCNH2: c. 94G>A (p.A32T) in the proband and his mother, confirming maternal inheritance. The variant was absent in the proband′s younger brother, father, maternal uncle, and maternal grandmother. ③ Both the proband and his mother were diagnosed of LQT2 subtype. The proband was treated with oral propranolol hydrochloride, while his mother received combined oral therapy with propranolol hydrochloride and mexiletine hydrochloride, both need taking lifelong medicine. The proband and his mother had been treated and followed up for over 3 years, and no syncope and cardiac events had occurred. The recheck of electrocardiogram showed that the proband′s QTc was shortened and his mother′s QTc returned to normal.

Family investigation facilitates early identification of congenital LQTS patient. Electrocardiogram examination with accurate QTc measurement is critical in syncope evaluation to prevent missed diagnoses of LQTS patient. Beta blockers are effective in the treatment of congenital LQT2 subtype patients.