Novel mutation in the KCNJ2 gene is associated with a malignant arrhythmic phenotype of Andersen-Tawil syndrome.

Abstract

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.

• Authors: E Fernlund, C Lundin, E Hertervig, O Kongstad, M Alders, P Platonov
• Journal: Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc (Ann Noninvasive Electrocardiol) Vol. 18 Issue 5 Pg. 471-8 (Sep 2013) ISSN: 1542-474X [Electronic] United States
• PMID: 24047492 (Publication Type: Case Reports, Journal Article)
• Copyright: ©2013 Wiley Periodicals, Inc.

Chemical References

• KCNJ2 protein, human
• Potassium Channels, Inwardly Rectifying

Topics

• Adolescent
• Adult
• Aged
• Andersen Syndrome (diagnosis, genetics, therapy)
• Child
• Defibrillators, Implantable
• Diagnosis, Differential
• Electrocardiography (methods)
• Female
• Genetic Testing (methods)
• Heart Arrest (genetics, prevention & control)
• Humans
• Male
• Middle Aged
• Phenotype
• Potassium Channels, Inwardly Rectifying (genetics)
• Tachycardia, Ventricular (genetics)
• Young Adult