**5. Genetic basis**

Short QT syndrome occurs mainly in an autosomal dominant pattern of inheritance with high phenotypic and genetic heterogeneity. To date, potential deleterious rare variants located in nine genes (*CACNA1C*, *CACNA2D1*, *CACNB2*, *KCNH2*,


*AE3: Anion exchanger; BrS: Brugada syndrome; CDSP: Systemic primary carnitine deficiency; GOF: gain-of-function; ICa: Voltage-gated calcium currents; IKr: Rapidly activating potassium currents; IKs: Slowly activating potassium currents; IK1: Inward rectifier potassium currents; LOF: loss-of-function; LQTS: Long QT syndrome; SQTS: Short QT syndrome.*

#### **Table 1.**

*Genes associated with Short QT Syndrome or Shorter than normal QT interval and its phenotypic overlap with the main arrhythmogenic syndromes.*

#### **Figure 3.**

*Diagram of the overlap between the genes associated with the short QT syndrome (SQTS) and the main channelopathies: Brs: Brugada syndrome; LQTS: long QT syndrome and CPVT: catecholaminergic polymorphic ventricular tachycardia.*

*KCNJ2*, *KCNQ1*, *SLC22A5*, *SLC4A3* and *SCN5A*) have been associated with SQTS (**Table 1**) [22]. However, only three genes (*KCNH2*, *KCNQ1* and *KCNJ2*) have been shown to cause SQTS definitively so far, and the *SLC4A3* gene presents moderate evidence [23]. The association of the other genes with SQTS remains controversial (**Figure 3**) [24].
