Test Catalog

Test ID: BRGGP    
Brugada Syndrome Multi-Gene Panel, Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

Providing a genetic evaluation for patients with a personal or family history suggestive of Brugada syndrome (BrS)

 

Establishing a diagnosis of a BrS, in some cases, allowing for appropriate management and surveillance for disease features based on the gene involved

 

Identifying variants within genes known to be associated with increased risk for disease features and allowing for predictive testing of at-risk family members

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes next-generation sequencing and supplemental Sanger sequencing to evaluate the genes tested on this panel.

 

Prior Authorization is available for this assay; see Special Instructions.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Brugada syndrome (BrS) is a genetic cardiac disorder characterized by ST segment elevation in leads V1-V3 on electrocardiography (EKG) with a high risk for ventricular arrhythmias that can lead to sudden cardiac death. BrS is inherited in an autosomal dominant manner and is caused by pathogenic variants in genes that encode cardiac ion channels. The diagnosis of BrS is established based on the characteristic EKG abnormality along with personal and family health history, and also requires exclusion of other causes including cardiac structural abnormalities, medications, and electrolyte imbalances.

 

BrS has also been called sudden unexplained nocturnal death syndrome (SUNDS) due to the tendency for syncope and sudden cardiac death to occur at rest or during sleep. The most common presentation of BrS is a male in his 40s with a history of syncopal episodes and malignant arrhythmias. However, presentation may occur at any age including infancy, where BrS may present as SIDS (sudden infant death syndrome). Published studies indicate that BrS is responsible for 4% to 12% of unexpected sudden deaths and for up to 20% of all sudden death in individuals with a structurally normal heart.

 

The prevalence of BrS in the general population is difficult to determine due to the challenges of diagnosing the condition. In Southeast Asia where SUNDS is endemic, the prevalence of BrS is estimated to be 1 in 2,000. Of note, men are 8 to 10 times more likely to express symptoms of BrS, but the disease affects females as well and both sexes are at risk for ventricular arrhythmia and sudden death.

 

Approximately 25% to 30% of BrS is accounted for by pathogenic variants in the genes known to cause the disorder, with the majority of cases attributed to the SCN5A gene. Although the majority of pathogenic variants identified to date have been detected by sequence analysis, large deletions in the SCN5A, SCN3B, CACNA1C, and KCNE3 genes have been reported in BrS. Genetic testing for BrS is supported by multiple consensus statements to confirm the diagnosis and identify at-risk family members. This is particularly important because the majority of patients with BrS are asymptomatic, but asymptomatic individuals may still be at increased risk for cardiac events. Pre- and posttest genetic counseling is an important factor in the diagnosis and management of BrS and is supported by expert consensus statements.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided. 

Interpretation Provides information to assist in interpretation of the test results

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Some individuals who have involvement of 1 or more of the genes on the panel may have a variant that is not identified by the methods performed (eg, promoter variants, deep intronic variants). The absence of a variant, therefore, does not eliminate the possibility of Brugada syndrome (BrS) or a related disorder.

 

Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a family history of BrS or a related disorder, it is often useful to first test an affected family member. Identification of a pathogenic variant in an affected individual allows for more informative testing of at-risk individuals.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genetic variants. Additionally, rare polymorphisms may be present that could lead to false-negative or false-positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis. If the patient has had an allogeneic blood or marrow transplant or a recent (ie, less than 6 weeks from time of sample collection) heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA.

 

Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time. Consultation with a genetics professional should be considered for interpretation of this result.

 

A list of benign and likely benign variants detected for this patient is available from the lab upon request.

 

Contact the laboratory if additional information is required regarding the transcript or human genome assembly used for the analysis of this patient's results.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Brugada R, Campuzano O, Brugada P, et al: Brugada Syndrome. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington, Seattle. Seattle, WA. 1993-2018. Updated 2016 Nov 17. Accessed June 2018. Available at www.ncbi.nlm.nih.gov/books/NBK1517/

2. Priori SG, Wilde AA, Horie M, et al: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm 2013;10:12:1932-1963

3. Ackerman MJ, Priori SG, Willems S, et al: HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies. Heart Rhythm 2011;8:1308-1339

4. Neilsen MW, Holst AG, Olesen SP, Olesen MS: The genetic component of Brugada syndrome. Front Physiol 2013;4:179:1-11

Special Instructions Library of PDFs including pertinent information and forms related to the test