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 based on the review of all reported SQTS cases to date.

SQTS is a genetically heterogeneous disease, with three ion channel genes identified as causative (SQT1–3, OMIM# 609620,# 609621,# 609622). SQT1 is associated with mutations in KCNH2 4 and SQT2 with mutations in KCNQ1. 5 Mutations in KCNJ2, the gene encoding the Kir2. 1 channels underlying the inward rectifier potassium current IK1, are linked to SQT3. 6 Overall, in only 30%(18/62) of the published SQTS cases can a causative mutation be identified, 2 indicating that additional genes likely play a role in the pathogenesis of SQTS. Kir2. 1 is part of a large family of inwardly rectifying potassium channels, and it is widely expressed with particularly high levels in the heart, brain, placenta, lung, and skeletal muscle. 7 This family of