Normally cardiac action potential duration shortens during activation of the sympathetic nervous system. This regulation of the cardiac action potential duration mediated by the beta adrenergic receptor activation requires the assembly of AKAP9 with the alpha sub unit (KCNQ1) of the Iks (slow component of delayed rectifier current) potassium channel. A mutation in AKAP9 (Yotiao) in the KCNQ1 binding domain reduces the interaction between KCNQ1 and Yotiao. This in turn reduces the cAMP induced phosphorylation of the channel and prevents the functional response of the Iks channel to cAMP. The final result is prolongation of the action potential and the QT interval due to delayed delpolarization by this S1570L-Yotiao mutation. [Chen L, Marquardt ML, Tester DJ, Sampson KJ, Ackerman MJ, Kass RS. Mutation of an A-kinase-anchoring protein causes long-QT syndrome. Proc Natl Acad Sci U S A. 2007;104:20990-5: http://www.ncbi.nlm.nih.gov/pubmed/18093912 ]

Short QT syndrome is characterized by consistently short QT intervals, usually below 300 msec, which does not lengthen with bradycardia. There is a propensity for sudden cardiac death and atrial fibrillation. Family history of sudden death may be forthcoming. Electrophysiologically short QT syndrome is characterized by short refractory periods and inducible VF (ventricular fibrillation) at EP (electrophysiological) study.

Shortening of QT interval can occur in tachycardia, hyperthermia and hypercalcemia. Digoxin can also shorten the QT interval. These should be excluded before considering a diagnosis of short QT syndrome.

Treatment options for short QT syndrome are limited. Some have reported lengthening of QT interval with quinidine. Most patients with short QT syndrome and a risk of sudden cardiac death get an ICD (implantable cardioverter defibrillator) implanted.