Resuscitated sudden cardiac death in Andersen-Tawil syndrome

Abstract

Andersen-Tawil Syndrome (ATS) is an autosomal dominant or sporadic disorder characterized by ventricular arrhythmias, periodic paralysis and distinctive facial and skeletal dysmorphology [1-3]. ATS is notable for its variable penetrance (not all subjects manifest all three phenotypes) and variable expressivity (the severity of the expressed phenotype varies considerably). The neuromuscular manifestations of ATS consist of intermittent weakness, often in the setting of progressive interictal weakness. The distinctive physical characteristics include low-set ears, micrognathia, syndactyly, clinodactyly, short stature and scoliosis. Cardiac manifestations of ATS include QT and QU interval prolongation, prominent U waves, frequent premature ventricular contractions (PVCs), polymorphic ventricular tachycardia (VT) and bidirectional VT [3,4]. Although the burden of ventricular ectopy is often high in patients with ATS [5], degeneration into life-threatening arrhythmias is relatively uncommon [6]. Distinguishing individuals with stable, but frequent ventricular ectopy and those at risk for sudden cardiac death remains a challenge. Dominant-negative mutations in KCNJ2, the gene encoding the inward rectifier potassium channel Kir2.1, account for the majority of ATS cases. However, nearly 30% of ATS patients do not have an identifiable mutation in KCNJ2, confirming the genetic heterogeneity of this disorder [7]. Interestingly, there are no obvious phenotypic differences that distinguish individuals with and those without a mutation in KCNJ2. Likewise, it is not clear that patients with KCNJ2 mutations are at greater, lower or similar risk of life-threatening arrhythmias, compared to those who are KCNJ2-mutation negative. In this report, we present a 15-year-old female with KCNJ2-mutation negative ATS who experienced a life-threatening cardiac event with devastating clinical consequences.