Novel Mutation in the KCNJ2 Gene Is Associated with a Malignant Arrhythmic Phenotype of Andersen‐Tawil Syndrome

Background Andersen‐Tawil syndrome (ATS) is a rare inherited multisystem disorder associated with mutations in KCNJ2 and low prevalence of life‐threatening ventricular arrhythmias. Our aim was to describe the clinical course of ATS in a family, in which the proband survived aborted cardiac arrest (ACA) and genetic screening revealed a previously unknown mutation (c.271_282del12[p.Ala91_Leu94del]) in the KCNJ2 gene. Methods A cascade family screening was performed in a 5‐generation family after identification of the KCNJ2 mutation in the proband. Subsequently, 10 of 21 screened individuals appeared to be mutation carriers (median age 38 [range 10–75] years, 3 female).  Mutation carriers underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, and exercise stress test. Results (1) At baseline, 2 patients had survived ACA, 3 had syncope or presyncopal attacks, and 2 reported palpitations. Exercise‐induced nonsustained bidirectional ventricular tachycardia was documented in 4 patients, 2 received implantable cardioverter‐defibrillators (ICD) for primary prevention and 2 for secondary prevention. (2) During follow‐up, 1 primary prevention and 1 secondary prevention patient received in total 4 adequate ICD shocks. Life‐threatening ventricular arrhythmias were documented during childhood in 5 of 10 mutation carriers. (3) All mutation carriers presented with characteristic mild dysmorphic features. Only 1 patient suffered from periodic paralysis. All had normal serum potassium level at repeated assessments and none had any other extracardiac disease manifestation. Conclusion Our findings suggest that the novel KCNJ2 mutation is associated with a predominantly cardiac phenotype of Andersen‐Tawil syndrome with high propensity to life‐threatening ventricular arrhythmias presenting from childhood and young adulthood.