Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-24T12:13:56.007Z Has data issue: false hasContentIssue false
  • English
  • Français

Evaluating the survivor or the relatives of those who do not survive: the role of genetic testing

Published online by Cambridge University Press:  13 January 2017

David J. Tester  and
Michael J. Ackerman
David J. Tester
Affiliation:
Departments of Cardiovascular Diseases, Pediatrics and Molecular Pharmacology & Experimental Therapeutics, Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota, United States of America
Michael J. Ackerman*
Affiliation:
Departments of Cardiovascular Diseases, Pediatrics and Molecular Pharmacology & Experimental Therapeutics, Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota, United States of America
*
Correspondence to: M. J. Ackerman, MD, PhD, Long QT Syndrome Genetic Heart Rhythm Clinic, the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota United States of America. Tel: 507 284 0101; Fax: 507 284 3757; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The molecular millennium has bestowed clinicians and researchers with the essential tools to identify the underlying genetic substrates for thousands of genetic disorders, most of which are rare and follow Mendelian inheritance patterns. The genetic basis of potentially lethal and heritable cardiomyopathies and cardiac channelopathies has been identified and are now better understood. Genetic testing for several of these heritable conditions has made its transition from discovery through translation and have been commercially available clinical tests for over a decade. Now that clinical genetic testing is available more readily and delivers a disease-specific impact across the triad of medicine – diagnostic, prognostic, and therapeutic – it is important for the community of cardiologists to not only be familiar with the language of genomic medicine but to also be wiser users and even wiser interpreters of genetic testing so that wise decisions can be rendered for those patients and their families being evaluated with respect to the presence or absence of one of these potentially lethal yet highly treatable genetic disorders. The purpose of this review is to provide the reader with a foundational understanding of genetic testing in clinical cardiology. Here, we will present some benefits of genetic testing: indications for either post-mortem genetic testing for the major cardiomyopathies and channelopathies or pre-mortem genetic testing among the decedent’s surviving relatives; the need for careful interpretation of genetic testing results; the importance of genetic counselling; and some points on the ethical and societal implications of genetic testing.

Keywords

Geneticsgenetic testingarrhythmiacardiomyopathylong QT syndrome
Type
Original Articles
Information
Cardiology in the Young , Volume 27 , Supplement S1: Sudden Cardiac Arrest in the Young: A Contemporary Perspective , January 2017 , pp. S19 - S24
Copyright
© Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Driscoll, DJ, Edwards, WD. Sudden unexpected death in children and adolescents. J Am Coll Cardiol 1985; 5: 118B–121B.CrossRefGoogle ScholarPubMed
2. Liberthson, RR. Sudden death from cardiac causes in children and young adults. N Engl J Med 1996; 334: 1039–1044.CrossRefGoogle ScholarPubMed
3. Tester, DJ, Ackerman, MJ. Genetic testing for potentially lethal, highly treatable inherited cardiomyopathies/channelopathies in clinical practice. Circulation 2011; 123: 1021–1037.CrossRefGoogle ScholarPubMed
4. Tester, DJ, Ackerman, MJ. Genetic testing for cardiac channelopathies: ten questions regarding clinical considerations for heart rhythm allied professionals. Heart Rhythm 2005; 2: 675–677.CrossRefGoogle ScholarPubMed
5. Priori, SG, Napolitano, C. Role of genetic analyses in cardiology: part I: Mendelian diseases: cardiac channelopathies. Circulation 2006; 113: 1130–1135.CrossRefGoogle ScholarPubMed
6. Ackerman, M, Priori, S, Willems, S, et al. 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). Heart Rhythm 2011; 8: 1308–1339.CrossRefGoogle ScholarPubMed
7. Gollob, M, Blier, L, Brugada, R, et al. Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol 2011; 27: 232–245.CrossRefGoogle Scholar
8. Bos, JM, Towbin, JA, Ackerman, MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol 2009; 54: 201–211.CrossRefGoogle ScholarPubMed
9. Shimizu, W. Clinical impact of genetic studies in lethal inherited cardiac arrhythmias. Circ J 2008; 72: 1926–1936.CrossRefGoogle ScholarPubMed
10. Ruan, Y, Liu, N, Napolitano, C, Priori, SG. Therapeutic strategies for long-QT syndrome: does the molecular substrate matter? Circ Arrhythm Electrophysiol 2008; 1: 290–297.CrossRefGoogle ScholarPubMed
11. Tester, DJ, Ackerman, MJ. Genetic testing. In Gussak I, Antzelevitch C, eds Electrical Diseases of the Heart: Genetics, Mechanisms, Treatment, Prevention. Springer, London, 2008, p 444–458.CrossRefGoogle Scholar
12. Kapa, S, Tester, DJ, Salisbury, BA, et al. Genetic testing for long-QT syndrome distinguishing pathogenic mutations from benign variants. Circulation 2009; 120: 1752–1760.CrossRefGoogle ScholarPubMed
13. Kapplinger, JD, Landstrom, AP, Bos, JM, Salisbury, BA, Callis, TE, Ackerman, MJ. Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise. J Cardiovasc Transl Res 2014; 7: 347–361.CrossRefGoogle ScholarPubMed
14. Kapplinger, JD, Landstrom, AP, Salisbury, BA, et al. Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise. J Am Coll Cardiol 2011; 57: 2317–2327.CrossRefGoogle ScholarPubMed
15. Tester, DJ, Valdivia, C, Harris-Kerr, C, et al. Epidemiologic, molecular, and functional evidence suggest A572D-SCN5A should not be considered an independent LQT3-susceptibility mutation. Heart Rhythm 2010; 7: 912–919.CrossRefGoogle Scholar
16. Ackerman, MJ. Genetic purgatory and the cardiac channelopathies: exposing the variants of uncertain/unknown significance (VUS) issue. Heart Rhythm 2015; 12: 2325–2331.CrossRefGoogle Scholar
17. Charron, P. Clinical genetics in cardiology. Heart 2006; 92: 1172–1176.CrossRefGoogle ScholarPubMed
18. Hershberger, RE, Cowan, J, Morales, A, Siegfried, JD. Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Heart Fail 2009; 2: 253–261.CrossRefGoogle ScholarPubMed
19. Van Riper, M. Genetic testing and the family. J Midwifery Womens Health 2005; 50: 227–233.CrossRefGoogle ScholarPubMed
20. Tester, DJ, Ackerman, MJ. The role of molecular autopsy in unexplained sudden cardiac death. Curr Opin Cardiol 2006; 21: 166–172.CrossRefGoogle ScholarPubMed