Decreased inward rectification of Kir2.1 channels is a novel mechanism underlying the short QT syndrome

This editorial refers to ‘A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents’ by T. Hattori et al ., pp. 666–673, this issue. The short QT syndrome (SQTS) is a recently recognized cardiac channelopathy characterized by a shortened QT interval in the electrocardiogram (ECG). It is associated with a high incidence of atrial fibrillation (AF), syncope, and sudden death in the absence of structural cardiac abnormalities. Gussak et al. first described the syndrome in 2000 within the context of an isolated case of sudden cardiac death in a young female and the presence of early-onset AF in a separate family.1 Cardiac workup demonstrated a structurally normal heart in affected individuals, but a remarkable short QTc interval on the ECG ranging between 248 and 300 ms. These first studies led to the emerging recognition of SQTS as a distinct clinical entity and were followed by reports on similar cases (reviewed in Gollob et al. 2). The diagnosis of SQTS is somewhat complicated as QT intervals overlap between affected cases and apparently healthy subjects. The presence of a short QT interval by itself is not always predictive of an increased arrhythmic risk and therefore should not invariably lead to a diagnosis of SQTS.3 To address this, Gollob et al. 2 recently proposed a set of formal diagnostic criteria …