Sudden Unexplained Nocturnal Death Syndrome; SUNDS

Brugada Syndrome is a cardiac conduction abnormality characterized by malignant ventricular arrhythmias, usually in an adult who reports a history of syncopal episodes. Sudden death is not uncommon. Classic cases have a typical ECG pattern, characterized by coved-type ST-segment elevation in the right precordial leads (so-called “type 1 Brugada ECG”), along with a personal history arrhythmia and/or a family history of premature sudden cardiac death or the characteristic ECG pattern.

Autosomal dominant inheritance with reduced penetrance. The primary gene associated with Brugada syndrome is SCN5A; mutations are identified in 15 to 30% of cases of individuals with type 1 Brugada ECG. Fewer than 5% of cases are accounted for by mutations in one of at least 11 other additional genes. 

NOTE: for BC patients, criteria must be met in order for testing to proceed.

1. Confirmation of diagnosis:

a. Persistent or provocable type I Brugada ECG pattern (ST elevation of a cove-shaped pattern in leads VI and V2); AND

• identified by EP Cardiologist (a cardiologist with further certification/training in cardiac electrophysiology);
• no structural heart disease
• no drugs known to cause Brugada-like ECG pattern

b. Test requested by Cardiologist or Medical Geneticist;

2. Family Testing:

• SCN5A mutation identified in index case
• First-degree relative (parent, sibling, child) of index case or other mutation-positive family member;
• Test requested by Medical Geneticist or Cardiologist

3. Prenatal testing (technically feasible but not routinely performed – contact MGL to discuss):

• Pregnancies to couples in which one person has confirmed Brugada syndrome and a known SCN5A mutation.
• Test requested by Medical Genetics

Bidirectional Sanger sequencing of the entire coding region and flanking intronic sequences of the SCN5A gene.

NM_198056.2 The ‘A’ within the initiation codon, ATG, is designated as nucleotide number 1.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., large genomic deletions/duplications, promoter mutations, regulatory element mutations).

For carrier/predictive testing due to a family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

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