Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity.

Abstract

Due to its varied and variable phenotypes, Andersen-Tawil syndrome (ATS) holds a unique place in the field of channelopathies. Patients with ATS typically present with the triad of periodic paralysis, cardiac arrhythmias, and developmental dysmorphisms. Although penetrance of ATS is high, disease expression and severity are remarkably variable. Mutations in KCNJ2 are the primary cause of ATS with 21 mutations discovered in 30 families. These mutations affect channel function through heterogeneous mechanisms, including reduced PIP2-related channel activation and altered pore function. Aside from KCNJ2-based ATS, the genetic basis of this disease in nearly 40% of cases is unknown. Other ATS genes likely share a common pathway or function with Kir2.1 or facilitate the activity of this ion channel. In this review, we explore hypotheses explaining the pathogenesis, expression, and variability of ATS.

• Authors: Matthew R Donaldson, Grace Yoon, Ying-Hui Fu, Louis J Ptacek
• Journal: Annals of medicine (Ann Med) Vol. 36 Suppl 1 Pg. 92-7 ( 2004) ISSN: 0785-3890 [Print] England
• PMID: 15176430 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Potassium Channels, Inwardly Rectifying

Topics

• Arrhythmias, Cardiac (genetics, physiopathology)
• Genetic Heterogeneity
• Humans
• Long QT Syndrome (genetics, physiopathology)
• Mutation
• Paralysis, Hyperkalemic Periodic (genetics, physiopathology)
• Potassium Channels, Inwardly Rectifying (genetics, physiology)
• Syndrome