Diagnostic and therapeutic challenges in Andersen-Tawil syndrome

Andersen-Tawil syndrome (ATS) is a rare autosomal dominant multisystem disorder characterised by ventricular arrhythmias, periodic paralysis, and dysmorphic features. However, marked phenotypic heterogeneity is observed, contributing to significant diagnostic delays. ATS is most commonly caused by loss-of-function variants in KCNJ2, which encodes the α-subunit of the inward rectifier potassium channel Kir2.1, resulting in impaired I_K1 currents. Impaired I_K1 destabilises terminal repolarisation and depolarisation kinetics, promoting prominent U waves, ventricular ectopy, and complex ventricular arrhythmias. Management remains challenging due to limited evidence and variable treatment response. β-blockers and flecainide are commonly used while implantable cardioverter-defibrillators are reserved for high-risk cases. Potassium supplementation and acetazolamide should be considered in selected patients with periodic paralysis. Given incomplete penetrance and absence of validated risk stratification tools, careful multidisciplinary evaluation and individualised management are essential.