Sudden death due to catecholaminergic polymorphic ventricular tachycardia following negative stress-test outcome: genetics and clinical implications
This paper discusses the case of a young boy who died suddenly during a football match. The victim’s personal and family medical histories were negative for cardiac events. He had undergone a cardiological investigation some months before his death, enabling him to participate in competitive sports. Only post-mortem molecular analysis allowed for a clearer determination of the most plausible cause of death, which was identified as inherited arrhythmogenic heart disease, known as catecholaminergic polymorphic ventricular tachycardia. It was possible to detect a novel, previously undescribed, variant in the RYR2 gene. This case report highlights the importance of a meaningful forensic multidisciplinary investigation in such cases, and also discusses possible medical malpractice claims.
KeywordsCatecholaminergic polymorphic ventricular tachycardia Rare variant Sudden cardiac death Stress electrocardiogram Provocation test
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human and animal studies
This article does not contain any studies with human participants or animals performed by any of the authors.
Oral informed consent was obtained from the family of the victim.
Declaration of interest
The Authors declare no sources of funding, direct or indirect, and any connection of any of the researchers with the tobacco, alcohol, pharmaceutical or gaming industries or anybody substantially funded by one of these organizations. The Authors declare also that there are no contractual constraints on publishing imposed by any funder.
- 14.Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, 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). Europace. 2011;13:1077–109.CrossRefGoogle Scholar
- 16.Exome Variant Server NGESPE. Seattle, WA. Available at http://evs.gs.washington.edu/EVS/. Accessed 1 Apr 2017.
- 20.Exome Aggregation Consortium (ExAC) Cambridge, MA, USA. http://exac.broadinstitute.org.
- 21.Exome Variant Server, NHLBI Exome Sequencing Project (ESP), Seattle, WA, USA. http://evs.gs.washington.edu/EVS/.
- 22.Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013;Chapter 7:Unit7.20.Google Scholar
- 36.Haugaa KH, Leren IS, Berge KE, Bathen J, Loennechen JP, Anfinsen OG, et al. High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening. Europace. 2010;12:417–23.CrossRefGoogle Scholar
- 45.Napolitano C, Priori SG, Bloise R. Catecholaminergic polymorphic ventricular tachycardia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, LJH B, et al., editors. GeneReviews(R). Seattle: University of Washington, Seattle University of Washington, Seattle ; 2004.GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reservedGoogle Scholar
- 46.Hayashi M, Denjoy I, Hayashi M, Extramiana F, Maltret A, Roux-Buisson N, et al. The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands. Europace. 2012;14:1344–51.CrossRefGoogle Scholar
- 50.Bauce B, Rampazzo A, Basso C, Bagattin A, Daliento L, Tiso N, et al. Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers. J Am Coll Cardiol. 2002;40:341–9.CrossRefGoogle Scholar