Short QT syndrome

Short QT syndrome
Specialty	Cardiology, medical genetics

Short QT syndrome is a genetic disease of the electrical system of the heart. It consists of a constellation of signs and symptoms, consisting of a short QT interval interval on EKG (≤ 300 ms) that does not significantly change with heart rate, tall and peaked T waves, and a structurally normal heart. Short QT syndrome appears to be inherited in an autosomal dominant pattern, and a few affected families have been identified.

Symptoms and signs

Short QT syndrome is inherited in an autosomal dominant pattern.

Individuals with short QT syndrome frequently complain of palpitations and may have unexplained syncope (loss of consciousness) Mutations in the KCNH2, KCNJ2, and KCNQ1 genes cause short QT syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the KCNH2, KCNJ2, or KCNQ1 gene increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of short QT syndrome. Short QT syndrome appears to have an autosomal dominant pattern of inheritance.

Due to the autosomal dominant inheritance pattern, most individuals will have family members with a history of unexplained or sudden death at a young age (even in infancy), palpitations, or atrial fibrillation.

Short QT syndrome is associated with an increased risk of sudden cardiac death, most likely due to ventricular fibrillation.

Diagnosis

Recent diagnostic criteria have been published out of the Arrhythmia Research Laboratory at the University of Ottawa Heart Institute from Drs. Michael H Gollob and Jason D Roberts (JACC 57:802-12).

The Short QT Syndrome diagnostic criteria is based on a point system as follows:

QTc in milliseconds

   <370                                              1
   <350                                              2
   <330                                              3

Jpoint-Tpeak interval

   <120                                              1

Clinical History

   Sudden cardiac arrest                             2
   Polymorphic VT or VF                              2
   Unexplained syncope                               1
   Atrial fibrillation                               1

Family History

   1st or 2nd degree relative with SQTS              2
   1st or 2nd degree relative with sudden death      1
   Sudden infant death syndrome                      1

Genotype

   Genotype positive                                 2
   Mutation of undetermined significance             1 
   in a culprit gene  

Patients are deemed high-probability (> or equal to 4 points), intermediate probability (3 points) or low probability (2 or less points).

Etiology

The etiology of short QT syndrome is unclear at this time. A current hypothesis is that short QT syndrome is due to increased activity of outward potassium currents in phase 2 and 3 of the cardiac action potential. This would cause a shortening of the plateau phase of the action potential (phase 2), causing a shortening of the overall action potential, leading to an overall shortening of refractory periods and the QT interval.

In the families afflicted by short QT syndrome, mutations have been described in three genes, KvLQT1, the human ether-a-go-go gene (HERG), and KCNJ2.

Treatment

Currently, the only effective treatment option for individuals with short QT syndrome is implantation of an implantable cardioverter-defibrillator (ICD).

A recent study has suggested the use of certain antiarrhythmic agents, particularly quinidine, may be of benefit in individuals with short QT syndrome due to their effects on prolonging the action potential and by their action on the I_K channels. While the use of these agents alone is not indicated at present, there may be benefit of adding these agents to individuals who have already had ICD implantation to reduce the number of arrhythmic events.

See also

• Long QT syndrome

References

• National Library of Medicine. Short QT syndrome