Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

NCT ID: NCT00999947

Last Updated: 2013-11-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 351 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2013-03-31

Brief Summary

The purpose of this trial is to study the genetic and phenotypic aspects of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C), and determine the impact of genetic testing in clinical practice.

Detailed Description

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.

Methods:

The study was approved by the Pitié-Salpétriêre Hospital ethical committee (CPPRB) and written informed consent was obtained from all participating individuals, recruited in France.

A cohort of 100 unrelated patients with ARVD/C will be recruited. Clinical evaluation will include clinical history, family history, blood sample for DNA analysis 12-lead ECG, signal-average ECG, 24-hour ambulatory ECG, transthoracic echocardiography, MRI and/or radionuclide scintigraphy, and contrast angiography when possible. A clinical diagnosis of ARVD/C is made according to the established European Society of Cardiology / International Society and Federation of Cardiology Task Force major and minor criteria (Task Force 1994).

All available relatives will be proposed for enrollment in the study with blood sample for DNA analysis and non invasive cardiac examination, including 12-lead ECG, signal-average ECG, and transthoracic echocardiography.

Mutational analysis of the five genes encoding desmosomal genes will be performed in all index cases (in plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, desmocollin-2). When mutations will be identified, available relatives will be analysed. In index cases without desmosomal mutation, additional analyses will be performed according to a candidate gene strategy and, when possible, through a genome wide approach and linkage analyses.

Expected results:

Determine the genetic origin in patients with ARVD/C whatever the familial context.

Determine a molecular strategy for routine genetic testing. Determine the impact of genetic testing as a diagnostic test in patients and relatives.

Determine the impact of genetics as a prognostic tool, through phenotype-genotype analyses.

Determine the natural evolution of the disease in relatives, and the penetrance.

Conditions

Cardiomyopathy; Arrhythmogenic Right Ventricular Dysplasia

Keywords

genetics; mutation screening; phenotype-genotype analysis; desmosomal genes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patient with DVDA diagnostic confirmed
• Acceptance even follow-up
• Informed consent

Exclusion Criteria

• Impossible to understand the notice information about study
• Not affiliated with social protection

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Charron, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Pitié-Salpêtrière Hospital

Locations

Pitié-Salpêtrière Hospital

Paris, , France

Countries

France

Other Identifiers

P051067

Identifier Type: -

Identifier Source: org_study_id