Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity.
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.
Donaldson
Matthew R
MR
Department of Human Molecular Biology and Genetics, University of Utah, Salt Lake City, USA.
Yoon
Grace
G
Fu
Ying-Hui
YH
Ptacek
Louis J
LJ
D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000503:physiopathology; D018740:Genetic Heterogeneity; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D020513:Paralysis, Hyperkalemic Periodic / Q000235:genetics* / Q000503:physiopathology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000502:physiology; D013577:Syndrome
D024661:Potassium Channels, Inwardly Rectifying