Variable penetrance of Andersen-Tawil syndrome in a family with a rare missense KCNJ2 mutation

Abstract

Andersen-Tawil syndrome is an autosomal dominant potassium channelopathy characterized by episodic flaccid muscle weakness (periodic paralysis), cardiac abnormalities (ventricular arrhythmias, prolonged QT interval, and prominent U waves), and characteristic skeletal features (low set ears, ocular hypertelorism, small mandible, fifth digit clinodactyly, syndactyly, short stature, scoliosis, and broad forehead).1 Mutations in the KCNJ2 gene on chromosome 17q23 are found in about 60% of the patients with Andersen-Tawil syndrome.2 In the absence of a genetic change in KCNJ2 , diagnosis of Andersen-Tawil syndrome is established by the presence of well-defined clinical findings. The distinctive clinical triad of Andersen-Tawil syndrome is present in 60%–80% of patients with KCNJ2 mutations.1,2 KCNJ2 encodes the pore-forming subunit of an inward-rectifying potassium channel protein, Kir2.1, helping in skeletal and cardiac muscle resting membrane potential stabilization. Mutations in this gene cause loss of function and dominant-negative suppression effects on the Kir2.1 protein, leading to disruption of the cardiac and skeletal muscle excitability.2,3 KCNJ2 mutations in Andersen-Tawil syndrome affect multiple tissues and results in a wide phenotypic variability causing diagnostic difficulties and delay.2 We describe the varied clinical characteristics of Andersen-Tawil syndrome in a Caucasian family (mother and her 2 daughters) with a rare missense mutation in KCNJ2 .