**1. Introduction**

Short QT syndrome is a rare inherited cardiac channelopathy characterized by the presence of short QT intervals and a high risk of malignant arrhythmias in the context of a structurally normal heart. Described more than 20 years ago by Gussak et al. [1], it was not until 2004 when the first genetic variants associated with the disease were published in *KCNH2* [2] *KCNQ1* [3] and *KCNJ2* [4]*,* named SQT1, SQT2 and SQT3, respectively. Since then, pathogenic variants have been described in six other genes associated with the disease, however, due to the low number of cases and the lack of a correct genotype-phenotype correlation, it is difficult to confirm the definitive pathogenic role of these genes as cause of SQTS. We aim to update current advances in SQTS, especially focused on genetics.

#### **2. Prevalence**

Today, it is difficult to establish the real prevalence of SQTS in the population, mainly due to the rarity of the disease and its possible underdiagnosis. The estimated prevalence is less than 1/10.000 in adults and about 1/2.000 in children and adolescents [5–8]. SQTS is potentially lethal for children in the first year of life, leading to a cardiac arrest rate close to 4%, making it one of the causes of sudden infant death syndrome (SIDS) [9].

#### **3. Diagnosis**

SQTS is diagnosed by the presence of a QTc ≤ 340 ms, or a QTc ≤ 360 ms when one of the following clinical criteria is met: detection of a clearly pathogenic genetic variant in one of the genes associated with the disease, family history of SQTS, family history of syncope or sudden cardiac death (SCD) before 40 years of age or survival of a ventricular tachycardia (VT) /ventricular fibrillation (VF) episode in the absence of heart disease [10]. However, its diagnosis can be challenging due to the large variability of the QT interval in healthy subjects.

Resting ECG should be performed at a normal heart rate when SQTS is suspected [11]. In addition, a stress test could be useful and a slope of the QT/HR ratio of less than −0.9 ms/beat/min could help distinguish affected subjects from healthy individuals [12]. Some studies support that QTc values should be adjusted in each population according to factors such as sex and age, and assessed in conjunction with other ECG criteria [13, 14]. For instance, a recent study in children and young adults demonstrated that a QTcB <316 ms, J-Tpeak cB < 181 ms (corrected by using Bazett's formula) and the presence of early repolarization (ER) could be indicative of SQTS in patients younger than 20 years of age [15]. Tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) could be part of the clinical evaluation, as systolic function may also be impaired and patients may present a dispersion of contraction in myocardium [16]. In contrast, invasive electrophysiological study (EPS) with programmed ventricular pacing is not recommended for SCD risk stratification [10] .
