ARVDNext

ARVDNextTM is a targeted panel for patients with arrhythmogenic right ventricular dysplasia (ARVD).  Often, ARVD is asymptomatic and sudden death is the first symptom. Therefore, genetic testing may be the most effective way of identifying at-risk individuals or confirming a diagnosis.

PrintPrint

ARVDNextTM is a targeted panel for patients with arrhythmogenic right ventricular dysplasia (ARVD).  Often, ARVD is asymptomatic and sudden death is the first symptom. Therefore, genetic testing may be the most effective way of identifying at-risk individuals or confirming a diagnosis.

ARVDNext is a next generation sequencing (NGS) and deletion/duplication panel of nine genes associated with ARVD: DSC2, DSG2, DSP, JUP, LMNA, PKP2, RYR2, TGFB3, TMEM43.  These genes are also included in the comprehensive inherited cardiomyopathy (CMNextTM), inherited arrhythmia (RhythmNextTM) and cardiovascular genetics (CardioNextTM) panels. 

Disease Name 
Arrhythmogenic right ventricular dysplasia (ARVD)
Disease Information 

ARVD occurs in approximately 1 in 1,000 individuals worldwide and is characterized by progressive fibrofatty replacement of the myocardium in the right ventricle. It is a leading cause of ventricular arrhythmia and sudden cardiac death in people under 35 years.  Severity of ARVD is highly variable within families, and the average age at diagnosis is 30 years of age.  ARVD is usually inherited in an autosomal dominant manner; a significant portion of ARVD is caused by compound heterozygous mutations or digenic mutations.  ARVD has also been seen in autosomal recessive conditions, such as Naxos disease and Carvajal syndrome.  Management for ARVD typically includes implantable cardioverter defibrillator (ICD) or pacemaker placement, which is essential in the prevention of sudden cardiac death. Treatment may also include specific medication use, with a small number of individuals requiring heart transplantation.

 

Genes Implicated in Arrhythmogenic Right Ventricular Dysplasia

genes implicated in arrythmogenic right ventricular dysplasia dsc2, dsp, pkp2, dsg2

Target Populations for ARVDNext

  • Patients with a definite, borderline or possible diagnosis of ARVD
  • Patients with a first-degree relative with a definite diagnosis of ARVD
  • Patients with a first-degree relative with ARVD confirmed pathologically at autopsy or during surgery
  • Patients with a first-degree relative with borderline/possible ARVD and a family history of sudden death before 35 years of age
Testing Benefits & Indication 
  • Clarify diagnosis and risk for sudden cardiac arrest
  • Target medical management and prevention of cardiac arrest and other complications
  • Adjust management in those with ARVD due to conditions like Naxos disease and Carvajal syndrome
  • Offer family members genetic testing (for a familial mutation) and implement medical surveillance to only those that need it
  • Reduce healthcare costs, resources, and anxiety for families
Test Description 

ARVDNext includes 9 genes associated with ARVD: DSC2, DSG2, DSP, JUP, LMNA, PKP2, RYR2, TGFB3, and TMEM43.  These genes are also included in the comprehensive inherited cardiomyopathy (CMNext), inherited arrhythmia (RhythmNext), and cardiovascular genetics (CardioNext) panels. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, followed by polymerase chain reaction (PCR) and NGS. Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Suspect variant calls are verified by Sanger sequencing.  This assay targets all coding domains, and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. Gross deletion/duplication analysis for available genes is performed utilizing a targeted chromosomal microarray.

Mutation Detection Rate 

50-60% of patients with a diagnosis of ARVD have a mutation in one of the ARVDNext genes (clinical sensitivity). ARVDNext can find >99.9% of described mutations in the included genes, when present (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above on this page.

Turnaround Time 
TEST CODE TEST NAME TURNAROUND TIME (WEEKS)
8904 ARVDNext 4-5 
8886 CMNextTM 4-5 
8887 CMNext + TTN 4-5 
8900 RhythmNextTM 4-5 
8910 CardioNextTM 4-5 
8911 CardioNext + TTN 4-5 
9520 CustomNext-Cardio
Up to 85 cardiovascular genes of your choice
4-5 weeks

 

Specialty 
Genes 
DSG2
DSP
DSC2
JUP
LMNA
PKP2
TGFB3
TMEM43
RYR2
Tests 
References 

1. Adapted from Ackerman MJ, et al. HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies. Heart Rhythm. 2011 Aug;8(8):1308-39. 

2. McNally E, MacLeod H, Dellefave-Castillo L. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. 2005 Apr 18 [Updated 2014 Jan 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.