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

BACKGROUND: 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.

CASE SUMMARY: 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.

DISCUSSION: 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.