Familial short QT syndrome (ORPHA:51083)
A rare, genetic cardiac rhythm disease characterized by a short QTc interval on the surface electrocardiogram (ECG) with a high risk of syncope or sudden death due to malignant ventricular arrhythmia.
Epidemiology
This extremely rare syndrome affects mainly young adults or infants and has been reported in nearly 80 families. The disease has been predominantly reported in males.
Clinical description
Whilst the disease may remain asymptomatic, the most common clinical presentation is a cardiac arrest (CA), with approximately 40% of patients suffering an episode of CA between birth and 40 years of age. Other symptoms include syncope and arrhythmias including atrial fibrillation, ventricular fibrillation (VF), supraventricular tachycardia (SVT), and polymorphic ventricular tachycardia. There is a high risk of recurrent arrhythmic events in symptomatic patients. The risk of sudden cardiac death (SDC) is highest in the first year of life and between 20 to 40 years.
Etiology
Mutations in the genes KCNQ1 (11p15.5), KCNH2 (7q36.1), and KCNJ2 (17q24.3), encoding cardiac ionic potassium channels, and the gene encoding the calcium channel, CACNA2D1 (7q21.11), have been identified in affected patients. 40% of patients do not have a genetic cause identified.
Diagnostic methods
According to the European Society of Cardiology Guidelines, SQTS is diagnosed by the presence of a corrected QT (QTc) interval less than or equal to 340 ms on resting 12-lead ECG or should be considered in the presence of a QTc less than or equal 360 ms and one or more of the following: a confirmed pathogenic mutation, a family history of SQTS, a family history of sudden death at young age (less than 40 years of age), or history of ventricular tachyarrhythmia/ventricular fibrillation (VT/VF) in the absence of heart disease. When a patient is diagnosed, clinical assessment is recommended in all family members, including an ECG in newborns.
Differential diagnosis
Differential diagnosis includes other repolarizing disorders such as Brugada syndrome and early repolarization syndrome. Of note, a few rare patients with Brugada syndrome have been reported to have a short QTc.
Genetic counseling
Transmission is autosomal dominant. Genetic counseling should be offered to affected families. First-degree relatives of an affected individual have a 50% risk of being affected. Sporadic cases have also been reported.
Management and treatment
Currently, an automatic implantable cardioverter-defibrillator (ICD) is recommended for patients who have experienced a sustained VT/VF episode or have survived an aborted cardiac arrest. However, ICD is complicated by a high probability of inappropriate ICD shocks, particularly in pediatric patients, and requires appropriate programming to prevent T-wave oversensing. Quinidine prophylaxis may be considered in patients where ICD is contraindicated/refused or in asymptomatic SQTS patients with a family history of SDC. Patients on quinidine should be carefully monitored for QT prolongation and possible pro-arrhythmic events.
Prognosis
The risk of sudden cardiac death is high, and a history of survived cardiac arrest at the initial presentation is a strong predictor of recurrent ventricular arrhythmias over the course of time.

                            Last update: 
                            December 2019


                            - Expert reviewer(s): 
                            Dr Isabelle DENJOY