Congenital Short QT Syndrome

Long QT intervals in the ECG have long been associated with sudden cardiac death. The congenital long QT syndrome was first described in individuals with structurally normal hearts in 1957.1 Little was known about the significance of a short QT interval. In 1993, after analyzing 6693 consecutive Holter recordings Algra et al concluded that an increased risk of sudden death was present not only in patients with long QT interval, but also in patients with short QT interval (<400 ms).2 Because this was a retrospective analysis, further evaluation of the data was not possible. It was not until 2000 that a short-QT syndrome (SQTS) was proposed as a new inherited clinical syndrome by Gussak et al.3 The initial report was of two siblings and their mother all of whom displayed persistently short QT interval. The youngest was a 17 year old female presenting with several episodes of paroxysmal atrial fibrillation requiring electrical cardioversion.3 Her QT interval measured 280 msec at a heart rate of 69. Her 21 year old brother displayed a QT interval of 272 msec at a heart rate of 58, whereas the 51 year old mother showed a QT of 260 msec at a heart rate of 74. The authors also noted similar ECG findings in another unrelated 37 year old patient associated with sudden cardiac death. A review on the subject including a discussion of proposed mechanisms appeared in 2002.4 The review highlighted the lack of rate-dependence of QT interval in cases in which QT abbreviation was constant and the negative correlation of QT with RR in cases in which an abnormally short QT was evident only at bradycardic rates. Among the principal gene candidates proposed to underlie these syndromes were gain of function mutations of IKr, IKs, IK-ACh and IK-ATP 4 (Figure 1). IK-ACh gain of function or other means by which the influence of the parasympathetic nervous system could be exaggerated was considered as the most likely mechanisms to explain the deceleration-dependent variant of the short QT syndrome.