Short QT syndrome (SQTS)

SQTS is exceedingly rare, with only a modest number of confirmed cases worldwide. Precise population‑level prevalence remains unknown due to the rarity of the condition, challenges in defining diagnostic cut‑offs, and frequent overlap with other inherited arrhythmia syndromes.

Short QT syndrome follows an autosomal dominant inheritance pattern, typically with high penetrance but variable clinical expressivity across families. Pathogenic variants can be transmitted from either parent, and affected individuals may show widely differing ages of onset or symptom severity. In some families, early‑onset atrial fibrillation may be the predominant phenotype. Cascade testing is therefore crucial to identify at‑risk relatives, especially as sudden cardiac death may occur before symptoms develop.

Diagnosis is based on a combination of ECG findings, clinical presentation, and exclusion of secondary causes such as hypercalcaemia, acidosis, drug effects, or carnitine deficiency. Although the diagnostic QTc threshold remains a matter of debate, current guidelines and expert consensus statements generally regard a markedly shortened QTc (typically ≤320–340 ms) as strongly suggestive of SQTS, whereas QTc values up to 360 ms require additional supporting features such as a pathogenic variant, a family history of SQTS or sudden cardiac death, or documented atrial or ventricular arrhythmias in the absence of structural heart disease.

• Short QT syndrome is diagnosed based on the presence of a markedly shortened QT interval in conjunction with clinical and/or familial features. Although appropriate QTc cut-off values for SQTS remain debated, a QTc consistently below 320-340 ms is considered strongly suggestive, whereas QTc values up to 360 ms require additional supporting features, such as arrhythmic events, a family history of sudden cardiac death, or a pathogenic variant in an associated gene. Identifying the underlying pathogenic variant can confirm the diagnosis in patients with an appropriate clinical phenotype and supports the clinical suspicion; however, genetic findings must always be interpreted in the context of clinical and electrocardiographic features.
• A confirmed molecular diagnosis can inform individualised surveillance, risk stratification, and clinical management, although it is not a prerequisite for targeted medical care; specific measures are determined by the treating physicians in consultation with the affected individual.
• Identification of the familial pathogenic variant enables predictive testing of at-risk relatives, allowing targeted clinical evaluation and follow-up.

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