ABSTRACT
AIMS: Andersen-Tawil syndrome (ATS) is an uncommon form of channelopathy linked to mutations in the KCNJ2 gene. Currently, little is known about the long-term arrhythmic prognosis of this disease. METHODS AND RESULTS: We conducted a retrospective multicentre study in nine French hospitals. Patients were recruited only if they were KCNJ2 mutation carriers. Thirty-six patients (female n = 22, 61%) from 20 unrelated kindred were included with a mean follow-up of 9.5 ± 8.2 years. We found 12 distinct KCNJ2 mutations in the 20 probands. Three of them were novel. Thirteen patients (36%) experienced syncope and one patient was resuscitated from cardiac arrest before diagnosis. The mean QTc interval was 439 ± 57 ms and QUc was 642 ± 64 ms. All patients had normal ejection fraction. Holter recordings in 33 patients found 11 272 premature ventricular complexes (PVCs) per day on average, 25 patients had episodes of bigeminy, and 25 patients had polymorphic PVCs. Twenty-three patients (70%) had non-sustained polymorphic ventricular tachycardia (VT), and six sustained polymorphic VT. Only one patient presented with torsades de pointes. Patients were treated with beta-blocker (n = 20), beta-blocker and amiodarone (n = 2), beta-blocker and flecainide (n = 6), or acetazolamide (n = 6). Radiofrequency ablation was attempted in five patients without clinical success. An implantable cardiac defibrillator was implanted in three patients. During follow-up, none of the patients died, four patients experienced syncope under treatment, and one patient had non-fatal cardiac arrest. CONCLUSION: Despite a severe clinical presentation with a very high rate of ventricular arrhythmias, the arrhythmic prognosis of the ATS patients is relatively good under treatment.
Subject(s)
Andersen Syndrome/genetics , Mutation , Potassium Channels, Inwardly Rectifying/genetics , Adolescent , Adult , Aged , Andersen Syndrome/complications , Andersen Syndrome/diagnosis , Andersen Syndrome/physiopathology , Andersen Syndrome/therapy , Child , Child, Preschool , DNA Mutational Analysis , Electrocardiography , Female , France , Genetic Predisposition to Disease , Heart Arrest/genetics , Humans , Male , Middle Aged , Phenotype , Prognosis , Retrospective Studies , Syncope/genetics , Time Factors , Young AdultABSTRACT
INTRODUCTION: Progressive cardiac conduction defect (PCCD) is a frequent disease attributed to degeneration and fibrosis of the His bundle. Over the past years, gene defects have been identified demonstrating that PCCD could be a genetic disease. The aim of this study was to show a familial aggregation for PCCD using a genetic epidemiological approach to improve in fine genetic knowledge of the transmission of the disease. METHODS AND RESULTS: Using the French social security number, the authors have been able to determine the city of birth of the 6667 patients implanted with a pacemaker (PM) for PCCD between 1995 and 2005 in the western part of France. The authors then mapped the frequency of PM implantations for PCCD. A large heterogeneity of the frequency of the disease has been observed, with a frequency of 0.21% in the major city (Nantes) ranging up to 2.28% in specific parishes. Familial studies performed in the parishes with the highest frequency of the disease allowed the authors to identify five large families with PCCD. Clinical investigations demonstrated phenotype heterogeneity between families. Three patterns have been differentiated. CONCLUSIONS: This study demonstrates a disparate geographical repartition of the frequency of PM implantation in the area of the authors at least in part related to a hereditary factor. The identification of five large families affected by PCCD using epidemiological approach underlines the existence of a major genetic background in PCCD.
