ABSTRACT
BACKGROUND/PURPOSE: Andersen-Tawil syndrome type 1 is a rare autosomal dominant disease caused by a KCNJ2 gene mutation and clinically characterized by dysmorphic features, periodic muscular paralysis, and frequent ventricular arrhythmias (VAs). Although polymorphic and bidirectional ventricular tachycardias are prevalent, PVCs are the most frequent VAs. In addition, a "dominant" morphology with RBBB pattern associated with either superior or inferior axis is seen in most of the patients. Due to the limited efficacy of most antiarrhythmic drugs, catheter ablation (CA) is an alternative in patients with monomorphic VAs. Based on our experience, we aimed to review the arrhythmogenic mechanisms and substrates for VAs, and we analyzed the potential reasons for CA failure in this group of patients. METHODS: Case report and focused literature review. RESULTS: Catheter ablation has been reported to be unsuccessful in all of the few cases published so far. Most of the information suggests that VAs are mainly originated from the left ventricle and probably in the Purkinje network. Although identifying well-established and accepted mapping criteria for successful ablation of a monomorphic ventricular arrhythmia, papillary muscles seem not to be the right target. CONCLUSIONS: More research is needed to understand better the precise mechanism and site of origin of VAs in Andersen-Tawil syndrome patients with this particular "dominant" monomorphic ventricular pattern to establish the potential role of CA.
Subject(s)
Andersen Syndrome , Catheter Ablation , Tachycardia, Ventricular , Ventricular Premature Complexes , Humans , Andersen Syndrome/genetics , Andersen Syndrome/surgery , Andersen Syndrome/complications , Heart Ventricles/surgery , Ventricular Premature Complexes/surgery , Catheter Ablation/adverse effectsABSTRACT
Andersen-Tawil syndrome (ATS) is caused by mutations in KCNJ2 (Kir2.1). It remains unclear whether dilated cardiomyopathy (DCM) is a primary feature of ATS. We studied a proband with typical physical features of ATS plus DCM and moderate to severe left ventricular dysfunction (left ventricular ejection fraction = 30.5%). Genetic screening revealed a novel mutation in Kir2.1 (c.665T>C, p.L222S). Functional studies showed that this mutation reduced ionic currents in a dominant-negative manner. Suppression of ventricular arrhythmias with bisoprolol led to normalization of left ventricular size and function. We conclude that DCM is likely a secondary phenotype in ATS and is caused by high ventricular arrhythmia burden.
Subject(s)
Andersen Syndrome , Bisoprolol/administration & dosage , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Adult , Andersen Syndrome/diagnosis , Andersen Syndrome/genetics , Andersen Syndrome/physiopathology , Andersen Syndrome/surgery , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/etiology , Cardiomyopathy, Dilated/therapy , Electrocardiography/methods , Genetic Testing/methods , Humans , Male , Mutation , Potassium Channels, Inwardly Rectifying/genetics , Severity of Illness Index , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/prevention & control , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/therapyABSTRACT
INTRODUCTION: Andersen-Tawil syndrome (ATS) is a potassium channelopathy affecting cardiac and skeletal muscle. Periodic paralysis is a presenting symptom in some patients, whereas, in others, symptomatic arrhythmias or prolongation of QT in echocardiographic recordings will lead to diagnosis of ATS. Striking intrafamilial variability of expression of KCNJ2 mutations and rarity of the syndrome may lead to misdiagnosis. METHODS: We report 15 patients from 8 Polish families with ATS, including 3 with novel KCNJ2 mutations. RESULTS: All patients had dysmorphic features; periodic paralysis affected males more frequently than females (80% vs. 20%), and most attacks were normokalemic. Two patients (with T75M and T309I mutations) had aborted sudden cardiac death. An implantable cardioverter-defibrillator was utilized in 40% of cases. CONCLUSIONS: KCNJ2 mutations cause a variable phenotype, with dysmorphic features seen in all patients studied, a high penetrance of periodic paralysis in males and ventricular arrhythmia with a risk of sudden cardiac death.
Subject(s)
Andersen Syndrome/complications , Andersen Syndrome/genetics , Genetic Predisposition to Disease/genetics , Heart Diseases/etiology , Mutation/genetics , Potassium Channels, Inwardly Rectifying/genetics , Adolescent , Adult , Andersen Syndrome/surgery , Child , DNA Mutational Analysis , Defibrillators, Implantable , Echocardiography , Female , Heart Diseases/genetics , Heart Diseases/surgery , Humans , Longitudinal Studies , Male , Paralyses, Familial Periodic/etiology , Paralyses, Familial Periodic/genetics , Poland , Retrospective Studies , Young AdultABSTRACT
Andersen-Tawil syndrome is an uncommon inherited autosomal disorder characterized by a prolonged QT interval, periodic paralysis, and dysmorphic features. The deleterious effects of cardioplegia on periodic paralysis and cardiac arrhythmia are unknown, and no studies have reported the performance of cardiac surgery in patients with Andersen-Tawil syndrome. We present a case of successful cardiac surgery in a patient with Andersen-Tawil syndrome, without using cardioplegia.
