Genetic Therapy

To assess a physician’s expertise on the basis of whether the doctor checks a patient’s QT interval would be excessive, but the fact remains that in many cases, checking it saves lives. The author of a respected textbook on electrocardiography1 wrote, “The measurement of the QT interval has little usefulness” in 1957 — the same year in which Jervell and Lange-Nielsen published their first report on the association between QT-interval prolongation and sudden death in a family with congenital deafness,2 which was soon followed by similar findings reported by Romano and colleagues3 and by Ward4 in patients with normal hearing. In 1975, Romano–Ward syndrome and Jervell–Lange-Nielsen syndrome were grouped under the name long QT syndrome.5
Long QT syndrome is an uncommon disease of genetic origin with a documented prevalence of 1 in 2000 live births6; however, the actual prevalence is probably higher because the original prospective study, which involved 44,000 infants,6 did not include genotype-positive–phenotype-negative persons. The syndrome is characterized by prolongation of the QT interval on an electrocardiogram (ECG) obtained when the patient was at rest and by a propensity for life-threatening arrhythmias that occur mostly under conditions of physical or emotional stress.5,7 The clinical importance of the timely diagnosis of the syndrome stems from the fact that sudden cardiac death is often the first symptom, which makes remedying diagnostic or therapeutic errors impossible. As stated 50 years ago,5 given the high efficacy of current therapies, the existence of patients with undiagnosed — and therefore untreated — long QT syndrome is nowadays inexcusable; unfortunately, missed diagnosis is still too often the case.