Multidisciplinary Study of Right Ventricular Dysplasia
Condition: Heart Diseases; Arrhythmogenic Right Ventricular Dysplasia
MeSH terms: Heart Diseases; Arrhythmogenic Right Ventricular Dysplasia
Study type: Observational

Summary: 
      The purpose of this study is to investigate the cardiac, clinical, and genetic aspects of
      arrhythmogenic right ventricular dysplasia (ARVD), a progressive disorder that predominantly
      affects the right side of the heart and causes ventricular arrhythmias.
    

Detailed description: 
      BACKGROUND:

      ARVD is an uncommon disorder but is considered a major cause of sudden death and
      life-threatening arrhythmia, in particular in the young population. The prevalence of ARVD is
      unknown but is certainly underestimated because of the difficulties in obtaining a correct
      diagnosis. It appears to be particularly frequent in certain geographical areas, probably for
      a founder effect, such as in northeast Italy, where a large number of ARVD cases and families
      have been described. A noncontrolled study of the University of Padua reported a frequency of
      familial forms of about 30 percent, indicating the existence of a defective gene in a large
      proportion of cases. In the United States the frequency of the disease is unknown, but the
      number of cases seems to be increasing.

      The etiology of ARVD was unknown until very recently. The main hypothesis involved apoptotic
      mechanisms and, in some cases, a viral infection. However, in the last couple of years, two
      genes causing ARVD have been identified. The first one encodes plakoglobin, a protein of the
      cardiac junctions with adhesive and signaling functions. The second ARVD gene is the cardiac
      ryanodine receptor (RYR2), which has been characterized only very recently by Dr. Danieli's
      group. In fact, this discovery is so recent that in this study, RYR2 is still considered a
      potential candidate. The discovery of the first disease genes provides the basis for a
      candidate gene approach following the hypothesis of a "final common pathway." Thus, major
      candidates become genes involved in cell-cell adhesion and encoding ion channels.

      DESIGN NARRATIVE:

      This is a multidisciplinary, multicenter, collaborative study investigating the cardiac,
      clinical, and genetic aspects of ARVD. The specific aims are (1) to establish a North
      American ARVD Registry enrolling ARVD patients and their family members, based on
      standardized diagnostic test criteria, in a prospective longitudinal follow-up study; (2) to
      determine the genetic background of ARVD by identifying chromosomal loci and specific gene
      mutations associated with this disorder; (3) to determine the influence of the genotype on
      the clinical course of patients with ARVD and explore phenotype-genotype associations that
      will contribute to improved diagnosis, risk stratification, and therapy; and (4) to develop
      quantitative methods to assess right ventricular function in order to enhance the specificity
      and sensitivity of ARVD diagnosis.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Referals to enrolling centers from communities
      
Biospecimen description: 
      Blood