Arrhythmic disorder mapped to chromosome 1q42-q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts
Arrhythmic disorder mapped to chromosome 1q42-q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts
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DOI：
10.1016/s0735-1097(99)00461-1
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发表时间：
1999-12-01
影响因子：
24
通讯作者：
Toivonen, L
中科院分区：
文献类型：
--
作者：
Swan, H;Piippo, K;Toivonen, L
目的 本研究的目的是提供恶性心律失常性疾病的临床和解剖学特征以及遗传背景。 背景 在两个家庭中检测到遗传性常染色体显性心脏综合征，在没有结构性心肌变化的情况下导致应激性多形性室性心动过速和晕厥。 方法 对两个有 6 名猝死受害者和 51 名在世成员的不相关家庭进行评估。进行静息和运动心电图（ECG）、超声心动图、磁共振成像（MRI）、电影血管造影、心内膜心肌活组织检查的显微镜检查以及IC类抗心律失常药物氟卡尼的药物测试。对基因位点进行遗传连锁分析。结果 24 名受影响个体中，10 人死亡，其中 6 例猝死，14 名幸存者出现疾病迹象。运动负荷试验在受影响的个体中诱发室性二联或多形性室性心动过速。三名在 10 岁之前接受检查的儿童在四年的随访中出现了心律失常。受影响受试者的静息心电图正常，但根据心率 (QTc) 调整的 QT 间期略有延长（430 +/- 18 与 409 +/- 19 毫秒，受影响与未受影响，p < 0.01）。服用氟卡尼不会引起家族性特发性心室颤动中出现的心电图异常。通过超声心动图、右心室电影血管造影和 MRI 检测，心室容积、收缩力和室壁测量结果均正常。组织病理学检查未发现纤维化或脓性浸润。 30岁时累计心脏死亡率为31%。疾病位点被分配到染色体 1q42-q43，两个家族的最大配对 lod 得分为 4.74。只有一名杂合子携带者在临床上未受影响，表明成年期疾病外显率较高。 结论 一种与染色体 1q42-q43 相关的独特心脏疾病会导致结构正常心脏中运动诱发的多形性室性心动过速，并且具有高度恶性。延迟的临床表现需要反复进行运动心电图检查，以确保家族中的年轻人得到诊断。 (C) 1999 年由美国心脏病学会发布。
OBJECTIVES The purpose of this study was to provide clinical and anatomical characteristics as well as genetic background of a malignant arrhythmogenic disorder.BACKGROUND An inherited autosomally dominant cardiac syndrome causing stress-induced polymorphic ventricular tachycardia and syncope in the absence of structural myocardial changes was detected in two families.METHODS Two unrelated families with six victims of sudden death and 51 living members were evaluated. Resting and exercise electrocardiograms (ECG), echocardiography, magnetic resonance imaging (MRI), cineangiography, microscopic examination of endomyocardial biopsies and a drug testing with a class IC antiarrhythmic agent flecainide were performed. A genetic linkage analysis was carried out to map the gene locus.RESULTS Of the 24 affected individuals, 10 had succumbed with six cases of sudden death, and 14 survivors showed evidence of disease. Exercise stress test induced ventricular bigeminy or polymorphic ventricular tachycardia in affected individuals. Three children initially examined before 10 years of age developed arrhythmias during a four-year follow-up. Resting ECGs were normal in affected subjects except a slight prolongation of the QT intervals adjusted for heart rate (QTc) (430 +/- 18 vs. 409 +/- 19 ms, affected vs. nonaffected, p < 0.01). Administration of flecainide did not induce ECG abnormalities encountered in familial idiopathic ventricular fibrillation. Ventricular volumes, contractility and wall measurements were normal by echocardiography, right ventricular cineangiography and MRI. Histopathological examination showed no fibrosis or farcy infiltration. The cumulative cardiac mortality by the age of 30 years was 31%. The disease locus was assigned to chromosome 1q42-q43, with a maximal pairwise lod score of 4.74 in the two families combined. Only one heterozygous carrier was clinically unaffected suggesting high disease penetrance in adulthood.CONCLUSIONS A distinct cardiac disorder linked to chromosome 1q42-q43 causes exercise-induced polymorphic ventricular tachycardia in structurally normal hearts and is highly malignant. Delayed clinical manifestation necessitates repeated exercise electrocardiography to assure diagnosis in young individuals of the families. (C) 1999 by the American College of Cardiology.