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Catecholaminergic Polymorphic Ventricular Tachycardia

The Catecholaminergic Polymorphic Ventricular Tachycardia Panel is a comprehensive NGS panel that can be used to confirm a clinical diagnosis of catecholaminergic polymorphic ventricular tachycardia or identify at-risk individuals. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia that is characterized by episodes of syncope that are typically brought on by emotional distress or exercise. Although affected individuals typically have normal heart rhythms at rest, stress can cause ventricular tachycardia which can lead to ventricular fibrillation and sudden death, even in individuals with no prior symptoms.

Prevalence

The exact prevalence of CPVT is unknown, although the estimated prevalence is 1 in 10,000 individuals (Napolitano et al, 2014).

Included Disorders

This panel includes genes associated with:

  • Catecholaminergic polymorphic ventricular tachycardia (CPVT)

Inheritance and Penetrance

CPVT is typically inherited in an autosomal dominant manner, although forms caused by mutations in TRDN and CASQ2 are inherited in an autosomal recessive manner. De novo mutations are estimated to occur in approximately 40% of cases caused by mutations in the RYR2 gene (Napolitano et al, 2004). CPVT exhibits reduced penetrance; the estimated penetrance of CPVT is approximately 80% (Napolitano et al, 2004). Approximately 30% of untreated individuals will experience cardiac arrest or sudden death (Napolitano et al, 2014).

Clinical Sensitivity

Disease causing mutations can be identified in approximately 70% of CPVT cases (Ackerman et al, 2011), with the majority of cases being caused by mutations in the RYR2 gene. The Catecholaminergic Polymorphic Ventricular Tachycardia Panel includes all of common genetic causes related to this disease.

Methodology and Analytical Sensitivity

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent intron/exon boundaries, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering. Analytical sensitivity of the assay is 99.5%.

Indications for Testing

  • Confirmation of a clinical diagnosis
  • Unexplained cardiac arrest
  • Arrhythmia suggestive of catecholaminergic polymorphic ventricular tachycardia
  • Risk assessment for asymptomatic family of members of proband with molecular diagnosis of CPVT

Included Genes (8)

ANK2 CASQ2
CALM1 KCNJ2
CALM2 RYR2
CALM3 TRDN

References

  1. Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Europace. 2011;13(8):1077-109.
  2. Napolitano C, Priori SG, Bloise R. Catecholaminergic Polymorphic Ventricular Tachycardia. 2004 Oct 14 [Updated 2016 Oct 13]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  3. Napolitano C, Bloise R, Memmi M, Priori SG. Clinical utility gene card for: Catecholaminergic polymorphic ventricular tachycardia (CPVT). Eur J Hum Genet. 2014;22(1)