Catecholaminergic Polymorphic Ventricular Tachycardia Caused by a Homozygous Pathogenic Variant in Calsequestrin 2 Gene

The article presents a clinical case of a 19-year-old patient with catecholaminergic polymorphic ventricular tachycardia caused by the pathogenic homozygous variant p.Ile193Asnfs*17 (rs397516643) in the CASQ2 gene, the early manifestations of which were recurrent syncope during emotional stress, supraventricular and polymorphic ventricular arrhythmias in the absence of structural changes in the heart. The article showed the evolution of heart rhythm disorders during the observation period. The authors discussed the issues of risk stratification for sudden cardiac death and the strategy for its prevention in this pathology.

1. Henriquez E, Hernandez E A, Mundla S R, Wankhade D H, Saad M, Ketha S S et al. Catecholaminergic Polymorphic Ventricular Tachycardia and Gene Therapy: a Comprehensive Review of the Literature. Cureus 2023;15(10):e47974. DOI:10.7759/cureus.47974.

2. Pérez‐Riera AR, Barbosa‐Barros R, de Rezende Barbosa MPC, Daminello‐Raimundo R, de Lucca AA Jr, de Abreu LC. Catecholaminergic polymorphic ventricular tachycardia, an update. Ann Noninvasive Electrocardiol. 2018;23:e12512. DOI:10.1111/anec.12512.

3. Abdullah NM, Ali A. RYR2 receptor gene mutation associated with catecholaminergic polymorphic ventricular tachycardia in children: a case report & literature review. Transl Pediatr 2024;13(2):359-369. DOI: 10.21037/tp-23-255.

4. Ng K., Titus E. W., Lieve K. V., Roston T. M., Mazzanti A., Deiter F. H. et al. An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of CASQ2-Catecholaminergic Polymorphic Ventricular Tachycardia. Circulation. 2020;142(10):932-947. DOI: 10.1161/CIRCULATIONAHA.120.045723.

5. Rizzi N, Liu N, Napolitano C, Nori A, Turcato F, Colombi B et al. Unexpected structural and functional consequences of the R33Q homozygous mutation in cardiac calsequestrin: a complex arrhythmogenic cascade in a knock in mouse model. Circ Res. 2008;103(3):298–306. DOI: 10.1161/CIRCRESAHA.108.171660.

6. Zaffran S., Kraoua L., Jaouadi H. Calcium Handling in Inherited Cardiac Diseases: A Focus on Catecholaminergic Polymorphic Ventricular Tachycardia and Hypertrophic Cardiomyopathy. Int. J. Mol. Sci. 2023;24(4),3365. DOI: 10.3390/ijms24043365.

7. Aggarwal A, Stolear A, Alam MM, Vardhan S, Dulgher M, Jang S-J, Zarich SW. Catecholaminergic Polymorphic Ventricular Tachycardia: Clinical Characteristics, Diagnostic Evaluation and Therapeutic Strategies. Journal of Clinical Medicine. 2024;13(6):1781. DOI:10.3390/jcm13061781.

8. Hayashi M, Denjoy I, Extramiana F, Maltret A, Buisson NR, Lupoglazoff JM et al. Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation. 2009;119(18):2426–34. DOI: 10.1161/CIRCULATIONAHA.108.829267.

9. Askarinejad A, Esmaeili S, Dalili M, Biglari A, Kohansal E, Maleki M et al. Catecholaminergic polymorphic ventricular tachycardia (and seizure) caused by a novel homozygous likely pathogenic variant in CASQ2 gene. Gene. 2024;895:148012. DOI: 10.1016/j.gene.2023.148012

10. Faggioni M, Kryshtal DO, Knollmann BC. Calsequestrin mutations and catecholaminergic polymorphic ventricular tachycardia. Pediatr Cardiol. 2012;33(6):959-67. DOI: 10.1007/s00246-012-0256-1.

11. Lahat H, Eldar M, Levy-Nissenbaum E, Bahan T, Friedman E, Khoury A et al. Autosomal recessive catecholamine- or exerciseinduced polymorphic ventricular tachycardia: Clinical features and assignment of the disease gene to chromosome 1p13-21. Circulation. 2001;103(23):2822–2827. DOI: 10.1161/01.cir.103.23.2822.

12. Al-Hassnan ZN, Tulbah S, Al-Manea W, Al-Fayyadh M. The phenotype of a CASQ2 mutation in a Saudi family with catecholaminergic polymorphic ventricular tachycardia. Pacing Clin Electrophysiol. 2013;36(5):e140-2. DOI: 10.1111/j.1540-8159.2012.03434.x.

13. de la Fuente S, Van Langen IM, Postma AV, Bikker H, Meijer A. A case of catecholaminergic polymorphic ventricular tachycardia caused by two calsequestrin 2 mutations. Pacing Clin Electrophysiol. 2008;31(7):916-9. DOI: 10.1111/j.1540-8159.2008.01111.x.

14. Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA et al. ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022;43(40):3997-4126. DOI: 10.1093/eurheartj/ehac262. PMID: 36017572.

15. Lieve KV, van der Werf C, Wilde AA. Catecholaminergic Polymorphic Ventricular Tachycardia. Circ J. 2016;80(6):1285-91. DOI: 10.1253/circj.CJ-16-0326.