**Abstract**

Short QT syndrome (SQTS) is an extremely rare inherited arrhythmogenic entity. Nowadays, less than 200 families affected worldwide have been reported. This syndrome is characterized by the presence of a short QT interval leading to malignant ventricular tachyarrhythmias, syncope and sudden cardiac death. It is one of the most lethal heart diseases in children and young adults. Both incomplete penetrance and variable expressivity are hallmarks of this entity, making it difficult to diagnose and manage. Currently, rare variants in nine genes have been associated with SQTS (*CACNA1C*, *CACNA2D1*, *CACNB2*, *KCNH2*, *KCNJ2, KCNQ1*, *SLC22A5*, *SLC4A3* and *SCN5A*). However, only pathogenic variants in four genes (*KCNH2*, *KCNQ1*, *KCNJ2* and *SLC4A3*) have been found to definitively cause SQTS. The remaining genes lack a clear association with the disease, making clinical interpretation of the variants challenging. The diagnostic yield of genetic tests is currently less than 30%, leaving most families clinically diagnosed with SQTS without a conclusive genetic diagnosis. We reviewed and updated the main genetic features of SQTS, as well as recent evidence on increasingly targeted treatment.

**Keywords:** sudden cardiac death, arrhythmias, short QT syndrome, genetics, QT interval variability
