Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Andersen-Tawil Syndrome
Introduction
Andersen-Tawil syndrome (ATS) is a clinically pleiotropic disorder resulting from mutations in an ion channel gene that modulates the most terminal portion of cardiac repolarization. ATS is fundamentally a disorder of ventricular repolarization. Although initially classified as long QT syndrome (LQTS) type 7, the noncardiac and cardiac clinical manifestations are distinct from classic LQTS and include dysmorphic features, periodic paralysis, and a high burden of ventricular ectopy. Additionally, the prominent U waves seen on the electrocardiogram (ECG) of the ATS population are not typical of more classic LQTS. The degree of repolarization derangement observed in this entity is directly related to the contribution of the disordered ion channel to the repolarization phase of the cardiac action potential (AP). This chapter discusses the most recent genetic, cellular, and clinical data underlying this unique ion channelopathy.
Andersen-Tawil Syndrome
In 1971 Andersen reported a series of patients with periodic skeletal muscle paralysis, ventricular ectopy, and dysmorphic features, the triad of clinical manifestations known as Andersen’s syndrome. Prolongation of the QT interval was incorporated as an important, but not exclusive, cardiac manifestation in subsequent larger studies of this disorder. The syndrome was renamed Andersen-Tawil syndrome (ATS) in recognition of the exceptional contributions of the clinical neurologist Rabi Tawil. Within the cardiovascular field, this disorder remained obscure until mutations in the K + channel gene KCNJ2 were identified as a cause of ATS. As is typical for rare diseases, the initial cohorts are always enriched for severe phenotypes; ATS was no exception, with most subjects displaying overt QTc prolongation, which was the reason for the designation LQTS7. KCNJ2 encodes the inward rectifier K + channel K ir 2.1, a component of the inward rectifier current I K1 . I K1 provides a substantial repolarizing current during the most terminal repolarization phase of the cardiac AP and is the primary conductance controlling the diastolic membrane potential. The notion that ATS is a relatively benign condition was recently challenged by a large natural history ATS study that demonstrated a significant risk for life-threatening events.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here
