What is Postmortem Genetic Testing?

Postmortem genetic testing is testing that is performed on a sample after an individual has died.  The goal of post mortem genetic testing is often to try to identify the cause of death and/or identify if blood relatives are at-risk for a genetic disease or sudden death. 

Genetic tests are a group of medical tests that search for alterations in chromosomes, genes, or biochemical metabolites.  There are numerous different genetic tests and choosing the appropriate test depends upon an individual's medical and family history.  Typically, genetic testing is ordered by a genetics specialist.  The gold standard for molecular genetic testing is EDTA blood or fresh frozen tissue (heart, liver and spleen).

Once an individual has died, additional issues are introduced which can make the genetic testing process more difficult.  Most commonly, these issues include sample collection/storage, insurance coverage and cost.

Young (< 40 years old) Sudden Death Is Often Genetic in Origin

• Up to 50% of sudden cardiac death (SCD) victims under age 35 years of age have no warning signs or family history of SCD. 1
• In approximately 30% of these cases there is no abnormality found in the heart on autopsy.
• Recent studies demonstrate that genetic testing helps to identify inherited cardiac disease in 25-35% of cases of SCD in the young. 1,2,3
• 15% of sudden infant death cases have been shown to have an underlying genetic cause. 4
• Post mortem genetic testing in sudden death cases is recommended by the Heart Rhythm Society and the European Heart Rhythm Association. 4

Why Should I Save a Sample?

The National Association of Medical Examiners (NAME) recommends retaining appropriate post mortem samples for genetic testing. Read More

In addition, genetic testing can:

• Identify or confirm the cause of the death.
• Confirm a suspected diagnosis.
• Provide the family with an explanation and closure.
• Allow other family members to be tested for a specific genetic disease that may be treatable.

Without a proper sample, genetic testing cannot be performed on deceased individuals.

When Should I Save a Sample for Potential Genetic Testing?

Diagnosis/Suspected Diagnosis/Cause of Death

• SIDS or SUID
• Cardiomyopathies (hypertrophic, idiopathic dilated, restrictive, arrhythmogenic, left ventricular noncompaction)
• Thoracic aneurysm
• Known genetic diagnosis

Autopsy Findings

• Macroscopic findings at autopsy of fatty infiltration of the liver

Symptoms

• Sudden unexplained death, especially if during exercise or during sleep (see sudden cardiac death statistics below)
• Unexplained acidosis, hypoglycemia, and/or hyperammonemia
• Lethargy, vomiting, fasting in the 48 hours prior to death

Circumstances of Death

• Drowning
• Single motor vehicle accident
• Unexplained seizure

Family History

• Family history of sudden death or inherited heart disease
• Family history of SIDS/SUID or sudden death at any age
• Family history of Reye syndrome
• Family history of known genetic diagnosis

What Samples Do I Save for Genetic Testing?

There are a wide range of samples that are appropriate to save for genetic testing. Learn More

How Much Does Postmortem Genetic Testing Cost? 

Genetic testing can be costly and is dependent upon the specific tests ordered. Cost of testing is determined by the laboratory. Coverage of testing through insurance can be difficult to secure and requires legwork by the ordering provider. Third-party payment by including the cost of post mortem genetic testing in the autopsy fee has been a successful practice.

Sample Letters of Medical Necessity

Cardiomyopathy PM Genetic Testing
Autopsy Negative PM Genetic Testing

What Information is Important to Share With the Surviving Family Members?

• Which sample(s) has been saved and how long it will be stored at the ME/coroner's office.
• Potential costs associated with post mortem genetic testing.
• This allows them to discuss the available options for the specimens with their managing physicians.
• The sudden unexplained death of a family member may warrant a medical evaluation for surviving family members.
• Example: If an inherited metabolic condition is suspected, then first-degree family members of the deceased individual could be advised to seek biochemical genetics evaluation.
• Genetic counselors are available to speak with the family.
• Genetic counselors can work with family members in a clinical setting to provide a risk assessment and help them navigate the available options for the saved DNA specimen.
• Information for families about post mortem genetic testing

Who Do I Contact if I Have Any Questions?

If you have questions regarding post mortem genetic testing, you can reach the NSGC Postmortem Group by emailing  postmortem@nsgc.org. A genetic counselor with expertise in post mortem genetic testing will reply to your email inquiry within 48 hours.

Genetic counselors have a unique set of skills which make them experts in guiding both patients and providers through the genetic testing process. To help you navigate the post mortem genetic testing process you can find a cardiovascular or metabolic genetic counselor through using NSGC's Find A Genetic Counselor tool.

For the most up to date list of labs offering cardiovascular testing or any other testing please visit www.genetests.org or www.ncbi.nlm.nih.gov/gtr/ and search on a disease to find out which labs offer testing. 

Additional Resources

• Information for Families about Postmortem Genetic Testing
• National Association of Medical Examiners (NAME) Position Paper: Retaining Postmortem Samples for Genetic Testing
• Barriers to Postmortem Genetic Testing
• Autopsy and Postmortem Sample Release Form
• Sudden Unexpected Death in Childhood
• Resources: Including a List of Patient and Family Support Groups; and Labs that Offer Cardiovascular Testing and DNA Banking
• 2009 Mayo Medical Labs Metabolic Autopsy Protocol (used in NJ and other states) 
• New Zealand Guidelines on Autopsy Practice
• Review of Postmortem Clinical Genetic Testing Sample Success Rates and Payors from Commercial Labs (Poster from the Heart Rhythm Society 2014 Conference)
• Sports Illustrated article on Wes Leonard's story
• Case Example
• Sudden Death in the Young Case Registry
• Additional Reading and References

Genealogy Testing

If you are interested in Genealogy testing (Genealogy is a DNA test looking for a persons’ ancestry/ethnicity), please contact the International Society of Genetic Genealogy: http://isogg.org/

References

1. Tester DJ, et al. The molecular autopsy: Should the evaluation continue after the funeral? Pediatr Cardiol. 2012 Mar 33(3):461-70. Epub 2012 Feb 4.
2. Behr 2003 et al “Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome.” Lancet. 2003 Nov 1, 362(9394):1457-9.
3. Tan, et al. (2003). “Sudden unexplained death: Heritability and diagnostic yield of cardiological and genetic examination in surviving relatives.” Circulation. 2005 Jul 12;112(2):207-13. Epub 2005 Jul 5.
4. Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin JA, Watkins H, Wilde A, Wolpert C, and Zipes DP. Heart Rhythm. 2011 Aug, 8(8):1308-39. 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)
5. Middleton O, Baxter S, Demo E, Honeywell C, Jentzen J, Miller F, Pinckard K, Reichard R, Rutberg J, Stacy C, and MacLeod H. NAME Position Paper: Retaining Postmortem Samples for Genetic Testing. Acad Forensic Pathol 2013 3 (2): 191-194.
6. MacLeod H, Demo E, Honeywell C and Rutberg J. Genetic Counselors: An Important Resource for Families Following a Young Sudden Cardiac Death. Acad Forensic Pathol 2013 3 (2): 183-190.
7. Loughrey CM, Preece MA, Green A. Sudden unexpected death in infancy (SUDI).  Journal of Clinical Pathology 2005;58(1):20-21. doi:10.1136/jcp.2004.020677
8. Mayo Medical labs Communique - The Metabolic Autopsy: Postmortem Screening in cases of Sudden, Unexpected Death
9. Gulino SP, Burns, K, Gunther, W, MacLeod H.  Acad Forensic Pathol. 2018 8(2): 347-391

Last Updated October 2018