Short QT syndrome is a new inherited disorder associated with familial atrial 
fibrillation and/or sudden death or syncope. To date, three different mutations 
in genes encoding cardiac ion channels (KCNH2, KCNQ1 and KCNJ2) have been 
identified as causing short QT syndrome. All mutations lead to a gain in 
function of the affected current (IK(r), IK(s )and IK(1)). The syndrome is 
characterized in the few patients identified so far by a shortened QT interval 
of less than 300-325 ms after correction for heart rate at rates below 80 beats 
per minute. However, no boundary or limit for the QT interval can yet be 
determined, as more knowledge about this disease is still restricted to a small 
patient population. Furthermore, the QT interval lacks adaptation to heart rate. 
The majority of patients exhibit shortened atrial and ventricular effective 
refractory periods and inducibility of ventricular fibrillation. Death already 
occurs in newborns, so the short QT syndrome may also account for deaths 
classified as sudden infant death syndrome. The therapy of choice in families 
with a history of sudden death or syncope seems to be the implantable 
cardioverter-defibrillator. Whether patients without a family history of sudden 
death or symptoms need a defibrillator cannot yet be answered, and requires 
further investigation. Pharmacologic treatment has only been investigated in 
patients with a mutation in KCNH2 (HERG), and it could be demonstrated that the 
mutant currents may be insufficiently suppressed by drugs that are targeted to 
block the specific current (e.g., sotalol or ibutilide) in patients with a 
mutation in the IK(r-)coding gene KCNH2 (HERG). Interestingly, in this specific 
patient population, quinidine proved to be efficient in prolonging the QT 
interval and normalizing the effective refractory periods. Implantable 
cardioverter-defibrillator therapy is associated with an increased risk of 
inappropriate therapies for T-wave oversensing, although this risk can be 
resolved by reprogramming implantable cardioverter-defibrillator detection 
algorithms.