Atypical Presentation of Andersen-Tawil Syndrome: Heart Failure with Reduced Ejection without Periodic Paralysis or Dysmorphic Features

Background: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder caused by variants in the KCNJ2 gene. It is associated with periodic paralysis, dysmorphic features and cardiac arrhythmias. The syndrome exhibits incomplete penetrance, leading to a broad spectrum of clinical manifestations, making diagnosis challenging.

Case description: A male in his mid-20s with class 3 obesity presented to the emergency department with a week-long history of worsening chest pain, orthopnoea and fatigue. His family history was significant for sudden cardiac death affecting both his mother and brother, with his father having died from complications of Wolff-Parkinson-White syndrome. Cardiovascular examination revealed an S3 heart sound and elevated brain natriuretic peptide levels at 875 pg/ml, with undetectable troponins; potassium level on admission was 3.6 mEq/l. An electrocardiogram showed normal sinus rhythm, first-degree heart block, left atrial enlargement, left bundle branch block and a prolonged QTc of 486 ms. A transthoracic echocardiogram demonstrated a 15-20% reduction in ejection fraction with global left ventricular hypokinesis and left atrial enlargement. Ultimately, he was diagnosed with non-ischaemic dilated cardiomyopathy and referred for genetic testing, which revealed a KCNJ2 variant. Shortly after discharge, he experienced a 55-second run of ventricular tachycardia, necessitating the placement of a single-chamber ICD. Currently, the patient remains on guideline-directed medical therapy and is listed for a heart transplant.

Conclusions: Dilated cardiomyopathy, although a rare manifestation in ATS, can profoundly increase the risk of fatal arrythmias, necessitating the need for a low threshold of suspicion, to ensure timely diagnosis and management.

Learning points: Andersen-Tawil syndrome (ATS) can present with heart failure with reduced ejection fraction, even without the typical triad of periodic paralysis, dysmorphic features and arrhythmias. Early genetic testing is essential for confirming ATS, especially in atypical cases with unexplained heart failure or arrhythmias.ATS has incomplete penetrance so it may present without the typical features, making diagnosis challenging and requiring a high suspicion in cases with unexplained arrhythmias or family history of sudden cardiac death.