Lupoglazoff Jean-Marc, Denjoy Isabelle, Villain Elisabeth, Fressart Véronique, Simon Françoise, Bozio André, Berthet Myriam, Benammar Nawal, Hainque Bernard, Guicheney Pascale
Pediatric Cardiology, Necker-Enfants-Malades (AP/HP), Paris, France. jean=
J Am Coll Cardiol. 2004 Mar 3;43(5):826-30. doi: 10.1016/j.jacc.2003.09.049.
We hypothesized that neonatal long QT syndrome (LQTS) with 2:1 atrioventricular block (AVB) could be related to HERG mutations.
Early onset of LQTS is rare but carries a high risk of life-threatening events such as ventricular arrhythmias and conduction disorders. There are no data on possible gene specificity.
We analyzed the characteristics and outcomes of 23 neonate probands from our LQTS population. Samples of DNA were available in 18 cases.
Long QT syndrome was diagnosed because of corrected QT interval (QTc) prolongation (mean QTc of 558 +/- 62 ms) and neonatal bradycardia attributable to sinus bradycardia (n = 8) or 2:1 AVB (n = 15). Symptoms included syncope (n = 2), torsades de pointes (n = 7), and hemodynamic failure (n = 6). Three infants with 2:1 AVB died during the first month of life. During the neonatal period, all living patients received beta-blockers (BB) and 13 had a combination of BB and permanent cardiac pacing. Under treatment, patients remained asymptomatic, with a mean follow-up of seven years. Mutations were identified in HERG (n = 8) and KCNQ1 (n = 8), and one child had three mutations (HERG, KCNQ1, and SCN5A). Conduction disorders were associated with LQT2, whereas sinus bradycardia was associated with LQT1.
Two-to-one AVB seems preferentially associated with HERG mutations, either isolated or combined. Long QT syndrome with relative bradycardia attributable to 2:1 AVB has a poor prognosis during the first month of life. In contrast, sinus bradycardia seems to be associated with KCNQ1 mutations, with a good short-term prognosis under BB therapy.
我们推测伴有2:1房室传导阻滞（AVB）的新生儿长QT综合征（LQTS）可能与HERG突变有关。
LQTS的早期发作较为罕见，但具有发生危及生命事件（如室性心律失常和传导障碍）的高风险。目前尚无关于可能的基因特异性的数据。
我们分析了来自我们LQTS队列的23例新生儿先证者的特征和结局。18例有DNA样本。
因校正QT间期（QTc）延长（平均QTc为558±62毫秒）以及由窦性心动过缓（n = 8）或2:1 AVB（n = 15）引起的新生儿心动过缓而诊断为长QT综合征。症状包括晕厥（n = 2）、尖端扭转型室速（n = 7）和血流动力学衰竭（n = 6）。3例患有2:1 AVB的婴儿在出生后第一个月内死亡。在新生儿期，所有存活患者均接受了β受体阻滞剂（BB）治疗，13例患者接受了BB与永久性心脏起搏的联合治疗。在治疗期间，患者保持无症状，平均随访7年。在HERG（n = 8）和KCNQ1（n = 8）中发现了突变，1名儿童有3种突变（HERG、KCNQ1和SCN5A）。传导障碍与LQT2相关，而窦性心动过缓与LQT1相关。
2:1 AVB似乎优先与孤立或合并的HERG突变相关。由2:1 AVB引起的伴有相对心动过缓的长QT综合征在出生后第一个月预后较差。相比之下，窦性心动过缓似乎与KCNQ1突变相关，并在BB治疗下具有良好的短期预后。
