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Abstract

Introduction:

Postmortem genetic testing (PMGT) can provide valuable information about an individual’s cause of death and potentially allow at-risk relatives to discern their risks for inherited cardiac disease. Postmortem genetic testing is most often successful with certain specimens.

Methods:

Investigators collected data on postmortem referrals to GeneDx, LLC for PMGT. Orders were reviewed and stratified based on provider, specimen type, and tests ordered.

Discussion:

This cohort included 601 deceased individuals referred for PMGT with a total of 673 genetic tests ordered from 247 different providers. The most common test categories ordered were arrhythmia (33.4%) and cardiomyopathy (29.3%). A likely pathogenic or pathogenic genetic variant was identified in approximately 15% of patients. Blood in EDTA was received for 21.6% of patients with a 95% success rate for completion of all test components. Blood samples in EDTA were most successful in completing PMGT, but sequencing was still successful in the majority of suboptimal specimens.

Conclusion:

The use of PMGT is increasing. Obtaining optimal samples (blood in EDTA) is important for successful completion of genetic testing. Obstacles may still exist for obtaining and storing ideal specimens. Continued efforts are needed for education and awareness around appropriate specimen types, storage and shipping of specimens, DNA banking, and overall availability of PMGT. In addition, access to resources such as supplies, proper storage conditions, DNA banking, and PMGT will allow for more opportunities to complete testing.

Keywords

Forensic pathology Sudden cardiac death (SCD)Sudden unexplained death (SUD)postmortem genetic testing (PMGT)Arrhythmia Cardiomyopathy

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References

Semsarian

Ingles

Wilde

. Sudden cardiac death in the young: the molecular autopsy and a practical approach to surviving relatives. Eur Heart J. 2015;36(21):1290–1296.

Ackerman

Atkins

Triedman

. Sudden cardiac death in the young. Circulation. 2016;133(10):1006–1026.

Williams

Manderski

Stewart

, et al. Lessons learned from testing cardiac channelopathy and cardiomyopathy genes in individuals who died suddenly: a two-year prospective study in a large medical examiner’s office with an in-house molecular genetics laboratory and genetic counseling services. J Genet Couns. 2020;29(2):293–302.

Campuzano

Sanchez-Molero

Allegue

, et al. Post-mortem genetic analysis in juvenile cases of sudden cardiac death. Forensic Sci Int. 2014;245:30–37.

Christiansen

Hertz

Ferrero-Miliani

, et al. Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting. Eur J Hum Genet. 2016;24(12):1797–1802.

Lahrouchi

Raju

Lodder

, et al. Utility of post-mortem genetic testing in cases of sudden arrhythmic death syndrome. J Am Coll Cardiol. 2017;69(17):2134–2145.

Middleton

Baxter

Demo

, et al. National association of medical examiners position paper: retaining postmortem samples for genetic testing. Acad Forensic Pathol. 2013;3(2):191–194.

Stattin

E-L

Westin

Cederquist

, et al. Genetic screening in sudden cardiac death in the young can save future lives. Int J Legal Med. 2016;130(1):59–66.

Tester

Medeiros-Domingo

Will

, et al. Cardiac channel molecular autopsy: insights from 173 consecutive cases of autopsy-negative sudden unexplained death referred for postmortem genetic testing. Mayo Clin Proc. 2012;87(6):524–539.

10.

Tang

Williams

Sampson

. Genetic testing in sudden unexpected natural death in the young: New York City office of Chief Medical Examiner’s experience and perspective. Forensic Sci Med Pathol. 2019;15(3):481–484.

11.

Priori

Wilde

Horie

, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013;10(12):1932–1963.

12.

Hofman

Tan

Alders

, et al. Yield of molecular and clinical testing for arrhythmia syndromes: report of 15 years’ experience. Circulation. 2013;128(14):1513–1521.

13.

Quenin

Kyndt

Mabo

, et al. Clinical yield of familial screening after sudden death in young subjects: the French experience. Circ Arrhythm Electrophysiol. 2017;10(9):e005236.

14.

Steinberg

Padfield

Champagne

, et al. Cardiac abnormalities in first-degree relatives of unexplained cardiac arrest victims: a report from the cardiac arrest survivors with preserved ejection fraction registry. Circ Arrhythm Electrophysiol. 2016;9(9):e004274.

15.

Wong

LCH

Roses-Noguer

Till

, et al. Cardiac evaluation of pediatric relatives in sudden arrhythmic death syndrome: a 2-center experience. Circ Arrhythm Electrophysiol. 2014;7(5):800–806.

16.

Webster

Olson

Schoppen

, et al. Cardiac evaluation of children with a family history of sudden death. J Am Coll Cardiol. 2019;74(6):759–770.

17.

Richards

Aziz

Bale

, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5): 405–423.

18.

Miller

Lee

Chung

, et al. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(8):1381–1390.

19.

Eddy

MacCormick

Chung

, et al. Identification of large gene deletions and duplications in KCNQ1 and KCNH2 in patients with long QT syndrome. Heart Rhythm. 2008;5(9):1275–1281.

20.

Tester

Benton

Train

, et al. Prevalence and spectrum of large deletions or duplications in the major long QT syndrome-susceptibility genes and implications for long QT syndrome genetic testing. Am J Cardiol. 2010;106(8):1124–1128.

21.

Stiles

Wilde

AAM

Abrams

, et al. 2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families. Heart Rhythm. 2021;18(1):e1–e50.

22.

Al-Khatib

Stevenson

Ackerman

, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2018;138(13):e73–e189.

23.

Liu

MacLeod

Webster

, et al. Genetic Counselors’ approach to PMGT after sudden death: an exploratory study. Acad Forensic Pathol. 2018;8(3):738–751.

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Postmortem Genetic Testing Is an Increasingly Utilized Tool in Death Investigation

Abstract

Introduction:

Methods:

Discussion:

Conclusion:

Keywords

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References

Supplementary Material