Background Andersen-Tawil Syndrome (ATS) is a rare channelopathy caused by mutations in the KCNJ2 gene that encodes the ubiquitously expressed Kir2.1 potassium channel.

Methods In our paper, we describe key findings in a large UK cohort of 52 patients, pertinent to the diagnosis and management of ATS. We report a new point prevalence of 0.105 per 100 000 (increased from 0.08 per 100 000).

Results While ATS has historically been considered a triad of episodic weakness, cardiac arrhythmias and dysmorphic features, we show that there is considerable variability to this phenotype. Pure cardiac or muscle phenotypes may exist. The absence of dysmorphic features does not exclude the diagnosis. Similarly, a normal long exercise test was seen in five patients.

Importantly, we identify that the phenotype includes a significant risk of cardiac morbidity and mortality with 13% of our cohort requiring cardiac defibrillator or pacemaker insertion and an additional 23% reporting syncope. Syncope has been recently associated with an increased risk of life threatening arhythmic events in this cohort. Severe fixed myopathy was seen in a quarter of our cohort with 14% requiring a wheelchair or gait aid.

Conclusions This is the largest multi-system study in ATS and provides key clinical insights to improve diagnosis, as well as management recommendations to address the potential for severe muscle weakness and cardiac morbidity and mortality.