The importance of comprehensive diagnostic work-up and genetic testing to reveal Andersen–Tawil syndrome—a case report

TL;DR

A case report shows how genetic testing helped diagnose a rare syndrome after a cardiac arrest, highlighting the importance of thorough diagnostics.

Contribution

Highlights the critical role of genetic testing in diagnosing Andersen–Tawil syndrome despite non-specific clinical presentations.

Findings

Genetic testing confirmed Andersen–Tawil syndrome in a patient with cardiac arrest and ambiguous symptoms.

The case demonstrates the syndrome's variable presentation and the need for comprehensive diagnostic work-up.

Pharmacological management remains uncertain, with unclear efficacy of beta-blockers and flecainide.

Abstract

Andersen–Tawil syndrome is characterized by a symptom triad of cardiac electrical abnormalities, periodic muscular paralysis, and distinct dysmorphic manifestations. A history of unexplained syncope has been associated with a more serious phenotype with increased risk of life-threatening arrhythmia. Due to the syndrome’s rarity and highly variable clinical presentation, diagnosis remains challenging.

This report highlights the importance of comprehensive diagnostic workup following a sudden cardiac arrest, particularly emphasizing the value of genetic testing. We present a 61-year-old male hypertensive patient who initially presented with a first-time syncopal episode. Initial investigations revealed ventricular ectopy exceeding 12 000 premature ventricular contractions, occasional QT prolongation of >500 ms, and mildly reduced left ventricular ejection fraction (50%). Outpatient diagnostic investigations did not yield a diagnosis. While awaiting ablation, the patient suffered from an out-of-hospital cardiac arrest and was successfully resuscitated after 17 min. Complete diagnostic work-up including guideline-adherent assessments and genetic testing eventually revealed Andersen–Tawil syndrome. The subsequent family evaluations supported the diagnosis.

Diagnosis was unexpected as the patient presented with isolated cardiac manifestations and a late onset of symptoms. Cardiomyopathy and primary arrhythmic disorders were relevant differential diagnoses and investigated during admission. No clinical assessment is pathognomonic for Andersen–Tawil syndrome, making genetic testing essential for establishing a definitive diagnosis. While historically characterized as a long QT variant, research suggests Andersen–Tawil syndrome is its own disease entity. Pharmacological management follows established channelopathy principles, though the protective efficacy of beta-blockers and flecainide remains uncertain in this syndrome.

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