Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients Caregivers Providers
Log In Ask a Question
PubMed This is a summary of 30 peer-reviewed journal articles Updated
Cardiology

What Is a Molecular Autopsy for Brugada Syndrome?

At a Glance

A molecular autopsy is post-mortem genetic testing used to uncover hidden causes of sudden, unexplained death, such as Brugada syndrome. By identifying mutations in genes like SCN5A, doctors can use targeted cascade screening to protect surviving family members from sudden cardiac arrest.

In this answer

4 sections

01

How Does a Molecular Autopsy Work?

02

The Role of SCN5A in Brugada Syndrome

03

Protecting Surviving Relatives

04

How to Advocate for a Molecular Autopsy

Navigating a sudden loss in your family is an overwhelming and heartbreaking experience. This page is designed to help families who have lost a loved one unexpectedly understand how a specific medical tool—a molecular autopsy—can uncover hidden genetic conditions and help keep surviving relatives safe.

A molecular autopsy is a specialized form of post-mortem testing that examines the DNA of someone who passed away suddenly and unexpectedly to look for genetic mutations that might have caused their death [1][2]. When a standard physical autopsy cannot find a clear cause—often the case with electrical heart conditions like Brugada syndrome—medical professionals can extract DNA from preserved blood or tissue samples to identify hidden genetic risks [3][4]. If a specific genetic mutation is found, surviving family members can undergo targeted genetic testing, known as cascade screening, to determine if they carry the same risk and need early protective care [3][5].

How Does a Molecular Autopsy Work?

In traditional autopsies, forensic pathologists look for physical abnormalities in the heart, like blockages or structural defects. However, conditions like Brugada syndrome affect the heart’s electrical system and leave the physical structure of the heart looking completely normal [4].

For a molecular autopsy, medical examiners or coroners use preserved tissue or blood samples to extract DNA [6][7]. However, how the sample is stored is critical. Standard autopsy chemicals, like formalin, can severely damage DNA. Families must often specifically request that the coroner save unpreserved, frozen tissue (like liver or spleen) or a specialized blood sample (such as blood in an EDTA tube or dried blood spot cards) for genetic testing [8].

A specialized laboratory then analyzes this DNA, looking at specific genes known to cause sudden cardiac death [9]. In about 20% to 30% of unexplained sudden deaths, this testing successfully identifies a genetic cause [4][10]. The results can take several weeks or even months to come back from the laboratory [11].

The Role of SCN5A in Brugada Syndrome

When Brugada syndrome is suspected, the testing panel focuses heavily on specific ion channel genes [12]. Ion channels act like tiny electrical gates in the heart’s cells, controlling the flow of electricity that regulates the heart’s rhythm. The most common genetic target is SCN5A, which is the primary gene associated with Brugada syndrome [13][14].

If a clear, disease-causing mutation is discovered, it provides a crucial roadmap [15]. Because Brugada syndrome is an inherited condition, first-degree relatives (parents, siblings, children) have a 50% chance of carrying the same mutation [16]. However, genetic results can be complex. Sometimes the test finds a Variant of Uncertain Significance (VUS)—a genetic change where it isn’t immediately clear if it causes the disease. These nuanced results require careful interpretation by an expert genetic counselor or cardiogeneticist [11][17].

Protecting Surviving Relatives

If a mutation is identified, immediate family members can undergo targeted genetic testing to see if they carry the same risk [3]. Crucially, even if the molecular autopsy does not find a specific genetic mutation, surviving family members still need clinical screening. Brugada syndrome can exist without a known genetic cause, so a “negative” genetic test does not guarantee the family is safe [18].

If you or your family members are found to be at risk for Brugada syndrome, early protective care includes:

  • Medical Screening: Having baseline electrocardiograms (ECGs) and potentially specialized drug provocation tests to see if the Brugada pattern appears on a heart monitor [19][20].
  • Fever Management: Fever is a known trigger for dangerous heart rhythms in Brugada syndrome. Knowing your risk means you must aggressively treat any fever with fever-reducing medications [19][21].
  • Medication Avoidance: Carriers must avoid specific prescription and over-the-counter (OTC) medications that can trigger Brugada syndrome. Safe and unsafe drugs are regularly updated on resources like BrugadaDrugs.org [22][23].
  • Preventative Treatments: In some cases, high-risk family members may need an implantable cardioverter-defibrillator (ICD) or other preventative measures to protect against sudden cardiac arrest [24][25].

How to Advocate for a Molecular Autopsy

Navigating the medicolegal system while grieving is incredibly difficult, but advocacy is often necessary to secure this vital testing.

  • Act Quickly: If a sudden loss has just occurred, immediately ask the medical examiner or coroner to retain unpreserved, frozen tissue or an EDTA blood sample specifically for DNA extraction and genetic testing [8][26].
  • Seek Specialists: In many areas, molecular autopsies are not routinely covered or performed by the coroner’s office [27]. You may need to connect the medical examiner’s office with a specialized clinical genetic counselor or cardiologist who can arrange for private genetic testing [3]. While the autopsy itself may be out-of-pocket, subsequent clinical evaluations and cascade screening for surviving family members are often covered by their own health insurance [28].
  • Get Clinical Care Now: Do not wait for the autopsy results (which can take months) to start protecting your family. First-degree relatives should undergo systematic clinical evaluations, including resting ECGs, with a cardiologist immediately [29][30].
  • Find Support: Processing a sudden loss while facing a potential genetic diagnosis is overwhelming. Consider seeking grief counseling and connecting with specialized support groups to help you and your family navigate this heavy burden [17].

Common questions in this guide

What is a molecular autopsy?
A molecular autopsy is a specialized post-mortem test that examines DNA to find genetic causes of sudden, unexpected death. It is primarily used when a standard physical autopsy cannot find a clear cause, which is often the case with electrical heart conditions.
What samples are needed for a molecular autopsy?
Standard autopsy chemicals, like formalin, severely damage DNA. Families must specifically ask the coroner or medical examiner to save unpreserved, frozen tissue or a specialized EDTA blood sample for genetic testing.
How does a molecular autopsy test for Brugada syndrome?
The test analyzes DNA extracted from unpreserved tissue or blood to look for mutations in specific ion channel genes. The most common genetic target checked for Brugada syndrome is the SCN5A gene.
What should my family do if the molecular autopsy is negative?
A negative genetic test does not guarantee safety, as Brugada syndrome can exist without a known genetic cause. First-degree relatives still need immediate clinical heart screening with a cardiologist, including resting electrocardiograms (ECGs).
What is cascade screening?
If a molecular autopsy identifies a disease-causing mutation, cascade screening is used to perform targeted genetic testing on immediate family members. It determines if surviving relatives carry the same mutation and require preventative care.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.If my family member's molecular autopsy comes back negative, what specific clinical screening tests should my siblings, children, and I undergo to ensure we are safe?
  2. 2.Can you refer us to a specialized cardiogeneticist or genetic counselor to help interpret the molecular autopsy results, especially if they find a Variant of Uncertain Significance (VUS)?
  3. 3.Are you able to coordinate with the medical examiner's office to ensure that unpreserved, frozen tissue or an EDTA blood sample is retained before it is damaged by standard autopsy chemicals?
  4. 4.If a pathogenic SCN5A mutation is found in our deceased family member, what is the process and timeline for getting cascade screening for the rest of the family?
  5. 5.What over-the-counter and prescription medications should our family avoid while we are waiting for our clinical screening and genetic test results?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

Related questions

Positive Brugada Gene With No Symptoms: What Is The Risk?Why Does Brugada Syndrome Cause Agonal Breathing at Night?What Dental Anesthesia is Safe for Brugada Syndrome?What Do Brugada ECG Type 1 and Type 2 Mean?Is Epicardial Ablation a Cure for Brugada Syndrome?Brugada Fainting vs Vasovagal Syncope: How to Tell?What to Do for a Fever With Brugada SyndromeCan a Heavy Meal Trigger a Brugada Syndrome Episode?What Happens During a Brugada Provocation Test?Brugada Syndrome vs. SUNDS: Are They the Same?Can You Drink Alcohol With Brugada Syndrome?Can I Exercise With Brugada Syndrome? Safety GuideHow to Check Medication Safety Using BrugadaDrugs.orgIs Brugada Syndrome Hereditary? | Inciteful MedWhy is Quinidine Used for Brugada Syndrome?How Is the Shanghai Score for Brugada Syndrome Calculated?What is a Brugada Phenocopy? ECG Pattern ExplainedWhen Is an ICD Required for Brugada Syndrome?

References

References (30)
  1. 1

    Molecular autopsy in sudden cardiac death.

    Campuzano O, Sarquella-Brugada G

    Global cardiology science & practice 2023; (2023(1)):e202308 doi:10.21542/gcsp.2023.8.

    PMID: 36890841
  2. 2

    A meta-analytic and meta-regression study of postmortem genetic analysis in sudden death: A step towards precision forensic genomics.

    Ponmani , Poovaragavan , Sangita M, Yadav J

    Forensic science international 2026; (383()):112893 doi:10.1016/j.forsciint.2026.112893.

    PMID: 41747495
  3. 3

    Genetic screening of relatives of decedents experiencing sudden unexpected death: medical examiner's office referrals to a multi-disciplinary cardiogenetics program.

    Siskind T, Williams N, Sebastin M, et al.

    Journal of community genetics 2022; (13(6)):629-639 doi:10.1007/s12687-022-00611-1.

    PMID: 36203036
  4. 4

    Findings of Uncertain Significance and a Family History of Sudden Death: Worth the FUSs?

    Ackerman MJ, Giudicessi JR

    Journal of the American College of Cardiology 2019; (74(6)):771-773 doi:10.1016/j.jacc.2019.06.042.

    PMID: 31395127
  5. 5

    Molecular autopsy in Chinese sudden cardiac death in the young.

    Kwok SY, Ho S, Shih FY, et al.

    American journal of medical genetics. Part A 2024; (194(11)):e63797 doi:10.1002/ajmg.a.63797.

    PMID: 38958565
  6. 6

    DNA isolated from formalin-fixed paraffin-embedded healthy tissue after 30 years of storage can be used for forensic studies.

    Vitošević K, Todorović M, Slović Ž, et al.

    Forensic science, medicine, and pathology 2021; (17(1)):47-57 doi:10.1007/s12024-020-00327-z.

    PMID: 33159288
  7. 7

    Practical tips to using formalin-fixed paraffin-embedded tissue archives for molecular diagnostics in a South African setting.

    van Deventer BS, du Toit-Prinsloo L, van Niekerk C

    African journal of laboratory medicine 2022; (11(1)):1587 doi:10.4102/ajlm.v11i1.1587.

    PMID: 35811747
  8. 8

    Benefits and outcomes of a new multidisciplinary approach for the management and financing of sudden unexplained death cases in a forensic setting in Switzerland.

    Neubauer J, Kissel CK, Bolliger SA, et al.

    Forensic science international 2022; (334()):111240 doi:10.1016/j.forsciint.2022.111240.

    PMID: 35276540
  9. 9

    Inherited Cardiac Arrhythmias and Channelopathies.

    Kline J, Costantini O

    The Medical clinics of North America 2019; (103(5)):809-820 doi:10.1016/j.mcna.2019.05.001.

    PMID: 31378327
  10. 10

    Yield of molecular autopsy in sudden cardiac death in athletes: data from a large registry in the UK.

    Finocchiaro G, Radaelli D, Johnson D, et al.

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2024; (26(2)) doi:10.1093/europace/euae029.

    PMID: 38289717
  11. 11

    Genetically determined cardiomyopathies at autopsy: the pivotal role of the pathologist in establishing the diagnosis and guiding family screening.

    Sheppard MN, van der Wal AC, Banner J, et al.

    Virchows Archiv : an international journal of pathology 2023; (482(4)):653-669 doi:10.1007/s00428-023-03523-8.

    PMID: 36897369
  12. 12

    Next-generation sequencing using microfluidic PCR enrichment for molecular autopsy.

    Raju H, Ware JS, Skinner JR, et al.

    BMC cardiovascular disorders 2019; (19(1)):174 doi:10.1186/s12872-019-1154-8.

    PMID: 31337358
  13. 13

    Update on Genetic Basis of Brugada Syndrome: Monogenic, Polygenic or Oligogenic?

    Campuzano O, Sarquella-Brugada G, Cesar S, et al.

    International journal of molecular sciences 2020; (21(19)) doi:10.3390/ijms21197155.

    PMID: 32998306
  14. 14

    The cardiac sodium channel gene SCN5A and its gene product NaV1.5: Role in physiology and pathophysiology.

    Veerman CC, Wilde AA, Lodder EM

    Gene 2015; (573(2)):177-87.

    PMID: 26361848
  15. 15

    Genetic Analysis of Arrhythmogenic Diseases in the Era of NGS: The Complexity of Clinical Decision-Making in Brugada Syndrome.

    Allegue C, Coll M, Mates J, et al.

    PloS one 2015; (10(7)):e0133037 doi:10.1371/journal.pone.0133037.

    PMID: 26230511
  16. 16

    Brugada syndrome: a fatal disease with complex genetic etiologies - still a long way to go.

    Wu Y, Ai M, Bardeesi ASA, et al.

    Forensic sciences research 2017; (2(3)):115-125 doi:10.1080/20961790.2017.1333203.

    PMID: 30483629
  17. 17

    Psychological adaptation to molecular autopsy findings following sudden cardiac death in the young.

    Bates K, Sweeting J, Yeates L, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2019; (21(6)):1452-1456 doi:10.1038/s41436-018-0338-4.

    PMID: 30327538
  18. 18

    Present Status of Brugada Syndrome: JACC State-of-the-Art Review.

    Brugada J, Campuzano O, Arbelo E, et al.

    Journal of the American College of Cardiology 2018; (72(9)):1046-1059 doi:10.1016/j.jacc.2018.06.037.

    PMID: 30139433
  19. 19

    Impact of clinical and genetic findings on the management of young patients with Brugada syndrome.

    Andorin A, Behr ER, Denjoy I, et al.

    Heart rhythm 2016; (13(6)):1274-82.

    PMID: 26921764
  20. 20

    Predicting ventricular arrhythmia inducibility in ajmaline-induced Brugada type I pattern: Validation of the dST-Tiso interval.

    Iacopino S, Fabiano E, Sorrenti P, et al.

    Journal of cardiovascular electrophysiology 2024; (35(9)):1747-1753 doi:10.1111/jce.16348.

    PMID: 38923783
  21. 21

    Coved and Saddleback ST-Segment Elevations: Brugada Phenocopy vs Brugada Syndrome.

    McCullough J, McCullough J, Gonzalez M

    Cureus 2022; (14(4)):e24338 doi:10.7759/cureus.24338.

    PMID: 35607564
  22. 22

    Use of Nonrecommended Drugs in Patients With Brugada Syndrome: A Danish Nationwide Cohort Study.

    Jespersen CHB, Krøll J, Bhardwaj P, et al.

    Journal of the American Heart Association 2023; (12(7)):e028424 doi:10.1161/JAHA.122.028424.

    PMID: 36942759
  23. 23

    Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a Long-Term Follow-Up.

    de Almeida Fernandes D, António N, Madeira M, et al.

    Cardiovascular drugs and therapy 2018; (32(1)):23-28 doi:10.1007/s10557-018-6770-5.

    PMID: 29372449
  24. 24

    Risk stratification of sudden cardiac death in Brugada syndrome: an updated review of literature.

    Darar C, Mohammed EA, Mohammed B, et al.

    The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology 2022; (74(1)):25 doi:10.1186/s43044-022-00267-9.

    PMID: 35404008
  25. 25

    Current perspectives on risk prediction and genetic basis of Brugada syndrome.

    Bhardwaj P, Stavnem D, Jacobsen SB, et al.

    Frontiers in cardiovascular medicine 2025; (12()):1722105 doi:10.3389/fcvm.2025.1722105.

    PMID: 41458990
  26. 26

    An updated approach to sudden cardiac death, the AECVP perspective.

    Michaud K, van der Wal AC, Banner J, et al.

    International journal of legal medicine 2021; (135(4)):1555-1557 doi:10.1007/s00414-021-02551-w.

    PMID: 33738570
  27. 27

    Implementation of Molecular Autopsy for Sudden Cardiac Death in Japan　- Focus Group Study of Stakeholders.

    Koike K, Nishigaki M, Wada T, Kosugi S

    Circulation journal : official journal of the Japanese Circulation Society 2022; (87(1)):123-129 doi:10.1253/circj.CJ-22-0265.

    PMID: 36372399
  28. 28

    Post-mortem genetic investigation in sudden cardiac death victims: complete exon sequencing of forty genes using next-generation sequencing.

    Fadoni J, Santos A, Cainé L

    International journal of legal medicine 2022; (136(2)):483-491 doi:10.1007/s00414-021-02765-y.

    PMID: 34984526
  29. 29

    Title not available

    Bhardwaj P, Winkel BG, Henriksen FL, et al.

    Ugeskrift for laeger 2024; (186(42)) doi:10.61409/V04240266.

    PMID: 39531018
  30. 30

    Evaluation After Sudden Death in the Young: A Global Approach.

    Gray B, Ackerman MJ, Semsarian C, Behr ER

    Circulation. Arrhythmia and electrophysiology 2019; (12(8)):e007453 doi:10.1161/CIRCEP.119.007453.

    PMID: 31422686

This page explains molecular autopsy and Brugada syndrome genetic testing for educational purposes. Always consult a genetic counselor or cardiologist for medical advice regarding your family's specific risk.

Get notified when new evidence is published on Brugada syndrome.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.