Genetic Study of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/ARVC), is an inherited myocardial disease that predominantly affects the right ventricle (RV) and the estimated prevalence in the general population ranges from 1 to 5 in 1000. It is characterized histopathologically by fibro-fatty myocardial replacement and clinically by ventricular arrhythmia that may lead to sudden death, especially in young people and athletes. Clinical diagnosis is based on diagnostic criteria proposed by the International Task Force of the European Society of Cardiology and International Society and Federation of Cardiology (Task Force 1994), but is often difficult due to a broad spectrum of clinical features and a lond period of concealed cardiac expression, with delayed diagnosis.

ARVC/D is familial in 30 to 50% and is typically transmitted as an autosomal dominant trait with variable penetrance. In the past years, the identification of causative mutations in plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin-2 (DSC2) has fostered the view that ARVC/D is a disorder of the desmosome and provided new insight into its pathogenesis.

The major recent advance in the molecular genetics of ARVD/C might lead to important clinical impact through early and correct diagnosis in patients and relatives, and through potential genotype-phenotype correlations. This key-issue requires first to clarify the optimal molecular strategy, and its efficiency. Such a systematic, detailed and comprehensive mutation screening study is not available until now.

Aim:

Study the genetic and phenotypic aspects of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C), and determine the impact of genetic testing in clinical practice.