Clinical and molecular genetics of the short QT syndrome.
OBJECTIVE
Sudden cardiac death in patients without structural heart disease remains a challenge in diagnostics and risk stratification. Genetically determined arrhythmias are a potential cause for a primary electrical disease. A recently discovered primary electrical disease is discussed.


RESULTS
The inherited short QT syndrome is a recently recognized genetic condition, which is associated with atrial fibrillation, syncope and/or sudden cardiac death. Attention has been focused on diagnostic ECG features, the identification of underlying mutations and mechanisms of arrhythmogenesis.


CONCLUSIONS
The short QT syndrome is clinically associated with atrial fibrillation, syncope and sudden cardiac death. A shortened QT interval (QTc <360 ms) and reduced ventricular refractory period together with an increased dispersion of repolarization constitute the potential substrate for reentry and life-threatening ventricular tachyarrhythmia. To date, gain-of-function mutations in KCNH2, KCNQ1, KCNJ2, encoding potassium channels and loss-of-function mutations in CACNA1C and CACNB2b, encoding L-type calcium channel subunits have been identified. The therapy of choice is the implantable cardioverter defibrillator in symptomatic patients. Quinidine has been shown to prolong the QT interval and to normalize the effective refractory periods of the atrium and ventricle in patients with short QT-1 syndrome.
Schimpf
Rainer
R
Ist Department of Medicine (Cardiology), University Hospital Mannheim, Mannheim, Germany. rainer.schimpf@med.ma.uni-heidelberg.de
Borggrefe
Martin
M
Wolpert
Christian
C
D001145:Arrhythmias, Cardiac / Q000150:complications / Q000235:genetics* / Q000628:therapy*; D001281:Atrial Fibrillation / Q000209:etiology; D020746:Calcium Channels, L-Type / Q000235:genetics; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D017147:Defibrillators, Implantable; D004562:Electrocardiography; D017353:Gene Deletion; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D016254:Mutagenesis, Insertional; D015221:Potassium Channels / Q000235:genetics; D018570:Risk Assessment; D013575:Syncope / Q000209:etiology; D013577:Syndrome
D020746:Calcium Channels, L-Type; D015221:Potassium Channels