Diagnostics

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Brugada Syndrome Panel

The Brugada Syndrome Panel is a comprehensive NGS panel that can be used to confirm a clinical diagnosis of Brugada syndrome or identify at-risk individuals.

Brugada syndrome is characterized by a dysfunction of the heart’s electrical system which causes ST segment abnormalities on ECG and can lead to irregular heart rhythms. Onset typically occurs around 40 years of age, although symptoms can present anytime between infancy and adulthood.  Individuals with Brugada syndrome may experience episodes of syncope or difficulty breathing, and are at increased risk for sudden cardiac death and sudden unexplained nocturnal death syndrome. Brugada syndrome accounts for approximately 4% to 12% of all sudden deaths and approximately 20% of deaths in patients with structurally normal hearts (Antzelevitch et all, 2002).

Prevalence

The exact prevalence of Brugada syndrome is unknown, although it is has been estimated to affect 1 in 2000 individuals in European populations (Gallagher et al, 2008), and may be higher in certain populations.

Included Disorders

This panel includes genes associated with:

  • Brugada syndrome

Inheritance and Penetrance

Brugada syndrome is typically inherited in an autosomal dominant manner, with the exception of the KCNE5 gene, which is inherited in an X-linked manner. Brugada syndrome exhibits reduced penetrance. One study of Brugada syndrome families with SCN5A mutations found penetrance ranging from 12.5% to 50% (Priori et al, 2000).

Clinical Sensitivity

Disease causing mutations can be identified in approximately 15-30% of Brugada syndrome cases (Kapplinger et al, 2010). The Brugada Syndrome Panel includes all of the 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 Brugada syndrome
  • Risk assessment for asymptomatic family of members of proband with molecular diagnosis of Brugada syndrome

Included Genes (10)

ABCC9 KCNE3
CACNA1C KCNH2
CACNB2 PKP2
GPD1L SCN10A
HCN4 SCN5A

Additions to Brugada Syndrome Panel

Emerging Evidence Genes (10)

Emerging evidence genes can also be added onto the comprehensive panel. These genes do not have a clear association with Brugada syndrome, but emerging evidence suggests that they may play a role in disease pathogenesis.

CACNA2D1 SCN1B
KCND3 SCN2B
KCNE5 SCN3B
KCNJ8 SLMAP
RANGRF TRPM4

References

  1. Antzelevitch C, Brugada P, Brugada J, et al. Brugada syndrome: a decade of progress. Circ Res. 2002;91(12):1114-8.
  2. Gallagher MM, Forleo GB, Behr ER, et al. Prevalence and significance of Brugada-type ECG in 12,012 apparently healthy European subjects. Int J Cardiol. 2008;130(1):44-8.
  3. Priori SG, Napolitano C, Gasparini M, et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation. 2000;102(20):2509-15.