Case report: State-of-the-art risk-modifying treatment of sudden cardiac death in an asymptomatic patient with a mutation in the SCN5A gene and a review of the literature

Petar Brlek; Eduard Stjepan Pavelić; Jana Mešić; Kristijan Vrdoljak; Andrea Skelin; Šime Manola; Nikola Pavlović; Jasmina Ćatić; Gordana Matijević; Josep Brugada; Dragan Primorac

doi:10.3389/fcvm.2023.1193878

Case report: State-of-the-art risk-modifying treatment of sudden cardiac death in an asymptomatic patient with a mutation in the SCN5A gene and a review of the literature

Front Cardiovasc Med. 2023 Sep 6:10:1193878. doi: 10.3389/fcvm.2023.1193878. eCollection 2023.

Authors

Petar Brlek^{1

2}, Eduard Stjepan Pavelić¹, Jana Mešić¹, Kristijan Vrdoljak¹, Andrea Skelin¹, Šime Manola³, Nikola Pavlović³, Jasmina Ćatić^{1

3}, Gordana Matijević¹, Josep Brugada⁴, Dragan Primorac^{1

2

5

6

7

8

9

10

11

12}

Affiliations

¹ St. Catherine Specialty Hospital, Zagreb, Croatia.
² School of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
³ Department for Cardiovascular Diseases, University Hospital Dubrava, Zagreb, Croatia.
⁴ Cardiovascular Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain.
⁵ Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
⁶ Medical School, University of Rijeka, Rijeka, Croatia.
⁷ Medical School, University of Mostar, Mostar, Bosnia and Herzegovina.
⁸ Medical School, University of Split, Split, Croatia.
⁹ Department of Biochemistry & Molecular Biology, The Pennsylvania State University, State College, PA, United States.
¹⁰ The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT, United States.
¹¹ Medical School REGIOMED, Coburg, Germany.
¹² National Forensic Sciences University, Gujarat, India.

Abstract

Brugada syndrome is a rare hereditary disorder characterized by distinct ECG findings, complex genetics, and a high risk of sudden cardiac death. Recognition of the syndrome is crucial as it represents a paradigm of sudden death tragedy in individuals at the peak of their lives. Notably, Brugada syndrome accounts for more than 20% of sudden cardiac deaths in individuals with structurally normal hearts. Although this syndrome follows an autosomal dominant inheritance pattern, it is more prevalent and severe in males. Diagnosis is primarily based on the characteristic ECG pattern observed in the right precordial leads. Mutations in the SCN5A gene, resulting in loss of function, are the most common genetic cause. We presented a 36-year-old proband with a family history of sudden cardiac death. Although the patient was asymptomatic for Brugada syndrome, his father had experienced sudden death at the age of 36. The proband was admitted to St. Catherine's Specialty Hospital where blood was taken and subjected to next-generation sequencing (NGS) using a "Sudden cardiac death" panel. The analysis identified a pathogenic variant in the SCN5A gene [c.4222G > A(p.Gly1408Arg)], which is associated with autosomal dominant Brugada syndrome. Based on the positive genetic test result, the patient was referred for further examination. ECG with modified precordial lead positioning confirmed the presence of the Brugada phenotype, displaying the type-2 and type-1 ECG patterns. Therefore, we made the diagnosis and decided to implant an implantable cardioverter-defibrillator (ICD) based on the results of broad genetic NGS testing, diagnostic criteria (ECG), and considering the high burden of sudden cardiac death in the patient's family, as well as his concerns that limited his everyday activities. This case shows that genetics and personalized medicine hold immense potential in the primary prevention, diagnosis, and treatment of Brugada syndrome and sudden cardiac death.

Keywords: Brugada syndrome; SCN5A; atrial fibrillation; implantable cardioverter-defibrillator; sudden cardiac death.

Publication types

Case Reports