Vincent G M, Timothy K W, Leppert M, Keating M
Department of Medicine, LDS Hospital, Salt Lake City, UT 84143.
N Engl J Med. 1992 Sep 17;327(12):846-52. doi: 10.1056/NEJM199209173271204.
The familial long-QT syndrome is characterized by a prolonged QT interval on the electrocardiogram, ventricular arrhythmias, and sudden death. It is not certain, however, that the length of the QT interval is a sensitive or a specific diagnostic criterion. Recently, we identified genetic markers on chromosome 11 that distinguished between carriers and noncarriers of the gene for the long-QT syndrome in three families. In this study, we compared the clinical features of carriers and noncarriers and assessed the diagnostic accuracy of the QT interval.
We obtained medical histories and electrocardiograms from 199 family members. QT intervals corrected for heart rate (QTc) were determined independently by two blinded investigators. Carriers of the long-QT gene (83 subjects) and noncarriers (116 subjects) were distinguished by genetic-linkage analysis.
Fifty-two of the carriers of the long-QT gene (63 percent) had a history of syncope, whereas four (5 percent) had a history of aborted sudden death. The QTc intervals of the gene carriers ranged from 0.41 to 0.59 second (mean, 0.49). By contrast, the QTc intervals of the noncarriers ranged from 0.38 to 0.47 second (mean, 0.42). On average, carriers of the gene for the long-QT syndrome had longer QTc intervals than noncarriers, but there was substantial overlap (in 126 of the 199 subjects, or 63 percent). The use of a QTc interval above 0.44 second as a diagnostic criterion resulted in 22 misclassifications among the 199 family members (11 percent). QTc intervals of 0.47 second or longer in males and 0.48 second or longer in females were completely predictive but resulted in false negative diagnoses in 40 percent of the males and 20 percent of the females.
In families affected by the long-QT syndrome, measurement of the QTc interval may not permit an accurate diagnosis. DNA markers make it possible to make a genetic diagnosis in some families, but not all gene carriers have symptoms.
家族性长QT综合征的特征是心电图上QT间期延长、室性心律失常和猝死。然而，QT间期的长度是否为敏感或特异的诊断标准尚不确定。最近，我们在11号染色体上鉴定出了遗传标记，可区分三个家族中长QT综合征基因的携带者和非携带者。在本研究中，我们比较了携带者和非携带者的临床特征，并评估了QT间期的诊断准确性。
我们获取了199名家庭成员的病史和心电图。两位不知情的研究者独立测定心率校正后的QT间期（QTc）。通过基因连锁分析区分长QT基因的携带者（83名受试者）和非携带者（116名受试者）。
长QT基因携带者中有52人（63%）有晕厥病史，而4人（5%）有猝死未遂病史。基因携带者的QTc间期为0.41至0.59秒（平均0.49秒）。相比之下，非携带者的QTc间期为0.38至0.47秒（平均0.42秒）。平均而言，长QT综合征基因的携带者QTc间期比非携带者长，但存在大量重叠（199名受试者中有126名，即63%）。将QTc间期大于0.44秒作为诊断标准，在199名家庭成员中导致22例误诊（11%）。男性QTc间期0.47秒或更长、女性QTc间期0.48秒或更长可完全预测，但导致40%的男性和20%的女性出现假阴性诊断。
在受长QT综合征影响的家族中，测量QTc间期可能无法进行准确诊断。DNA标记可使某些家族进行基因诊断，但并非所有基因携带者都有症状。
