心脏ryanodine受体(RyR2)功能获得突变导致儿茶酚胺能多形性室性心动过速(CPVT)。相反,RyR2功能丧失突变导致一种新的疾病实体,称为钙释放缺乏症(CRDS),其中可能包括RYR2相关的长QT综合征(LQTS)。重要的是,与CPVT不同,CRDS患者并不总是表现为运动或肾上腺素引起的室性心律失常,这排除了CRDS的诊断。在这里,我们报告一个男孩和他的父亲,他们都经历了运动诱发的心脏事件,并且拥有相同的RYR2E4107A变体。在男孩身上,运动应激试验(EST)和肾上腺素激发试验(EPT)未诱发室性心律失常.QTc略有延长(QTc:474ms),和EPT诱导的QTc延长(QTc基线:466ms,峰值:532ms,稳态:527毫秒)。相比之下,在他的父亲,QTc没有延长(QTc:417ms),EST和EPT均不诱导QTc延长。然而,EST诱导的多灶性室性早搏(PVC)双联和双向PVC对联。因此,他们表现出不同的临床表型:男孩表现出LQTS(或CRDS)表型,而他的父亲表现出CPVT表型。这些发现表明,除了改变的RyR2函数之外,其他不明因素,比如其他基因,表观遗传,和环境因素,和衰老,可能涉及不同的表型表现。考虑到单个RYR2变体可以引起CPVT和LQTS(或CRDS)表型,在CPVT和CRDS患者的级联筛查中,EST和EPT是不够的,需要进行遗传分析以确定危及生命的心律失常风险增加的个体.
Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.