Andersen-Tawil syndrome: clinical and molecular aspects

Int J Cardiol. 2013 Dec 5;170(1):1-16. doi: 10.1016/j.ijcard.2013.10.010.

Abstract

Andersen–Tawil syndrome (ATS) is a rare hereditary multisystem disorder. Ventricular arrhythmias, periodic paralysis and dysmorphic features constitute the classic triad of ATS symptoms. The expressivity of these symptoms is, however, extremely variable, even within single ATS affected families, and not all ATS patients present with the full triad of symptoms. ATS patients may show a prolongation of the QT interval,which explains the classification as long QT syndrome type 7 (LQT7), and specific neurological or neurocognitive defects. In ATS type 1 (ATS1), the syndrome is associated with a loss-of-function mutation in the KCNJ2 gene,which encodes the Kir2.1 inward rectifier potassium channel. In ATS type 2 (ATS2), which does not differ from ATS1 in its clinical symptoms, the genetic defect is unknown. Consequently, ATS2 comprises all cases of ATS in which genetic testing did not reveal a mutation in KCNJ2. The loss-of-function mutations in KCNJ2 in ATS1 affect the excitability of both skeletal and cardiac muscle, which underlies the cardiac arrhythmias and periodic paralysis associated with ATS. Thus far, the molecular mechanism of the dysmorphic features is only poorly understood. In this review, we summarize the clinical symptoms, the underlying genetic and molecular defects, and the management and treatment of ATS.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Andersen Syndrome / diagnosis*
  • Andersen Syndrome / genetics*
  • Andersen Syndrome / therapy
  • Animals
  • Humans
  • Molecular Sequence Data
  • Mutation / genetics
  • Potassium Channels, Inwardly Rectifying / genetics*

Substances

  • KCNJ2 protein, human
  • Potassium Channels, Inwardly Rectifying