The short QT syndrome constitutes a new clinical entity that is associated with 
a high incidence of sudden cardiac death, syncope, and/or atrial fibrillation 
even in young patients and newborns. Patients with this congenital electrical 
abnormality are characterized by rate-corrected QT intervals<320 ms. Missense 
mutations in KCNH2 (HERG) linked to a gain-of-function of the rapidly activating 
delayed-rectifier current I(Kr) have been identified in the first two reported 
families with familial sudden cardiac death. Recently, two further 
gain-of-function mutations in the KCNQ1 gene encoding the alpha-subunit of the 
KvLQT1 (I(Ks)) channel and in the KCNJ2 gene encoding the strong inwardly 
rectifying channel protein Kir2.1 confirmed a genetically heterogeneous disease. 
The possible substrate for the development of ventricular tachyarrhythmias may 
be a significant transmural dispersion of the repolarisation due to a 
heterogeneous abbreviation of the action potential duration. The implantable 
cardioverter defibrillator is the therapy of choice in patients with syncope and 
a positive family history of sudden cardiac death. However, ICD therapy in 
patients with a short QT syndrome has an increased risk for inappropriate shock 
therapies due to possible T wave oversensing. The impact of sotalol, ibutilide, 
flecainide, and quinidine on QT prolongation has been evaluated, but only 
quinidine effectively suppressed gain-of-function in I(Kr) with prolongation of 
the QT interval. In patients with a mutation in HERG, it rendered ventricular 
tachycardias/ventricular fibrillation non-inducible and restored the QT 
interval/heart rate relationship towards a normal range. It may serve as an 
adjunct to ICD therapy or as a possible alternative treatment, especially for 
children and newborns.