Brugada ECG pattern in hypertrophic cardiomyopathy: Brugada phenocopy or overlapping syndrome?
Introduction
The term phenocopy indicates a condition that imitates one produced by a gene and is also used for acquired Brugada-like ECG manifestations. Cases of Brugada phenocopies are increasingly reported in literature in different clinical settings, and their significance is not still fully understood. We describe two patients, from our Hospital in Carpi (Modena, Italy), with Hypertrophic Cardiomyopathy (HCM) and Brugada ECG pattern. Both patients carried the same pathogenic splicing mutation in MYBPC3 sarcomeric gene (encoding for the cardiac myosin-binding protein C) and no genetic mutation associated with Brugada Syndrome. To the best of our knowledge, Brugada ECG pattern has been only rarely reported in patients with hypertrophic cardiomyopathy.
Section snippets
Case #1
An asymptomatic 58-years-old Caucasian man had an incidental finding of spontaneous type 1 Brugada ECG (Fig. 1). His father suddenly died at age of 75, from unknown cause. Echocardiogram and cardiac magnetic resonance showed significant left ventricular hypertrophy (LVH) (Fig. 1B). Genetic analysis was performed with Trusight Cardio Sequencing kit (Illumina, San Diego, CA, USA) including genes associated with different cardiac diseases at risk of sudden cardiac death (SCD). A Pathogenic (P)
Case #2
A 60-years-old Caucasian man was diagnosed with genetically determined apical HCM and paroxysmal atrial fibrillation. The ECG (Fig. 2) showed a spontaneous type 1 Brugada pattern, in absence of any identifiable cause. His brother and his father were both affected by HCM and they suddenly died at age of 41 and 69, respectively. Genetic examination, using the Trusight Illumina Cardio Sequencing kit, showed a P splicing variant in MYBPC3 gene (c.1458-1G ≥ A), the same detected in case #1. Clinical
Discussion
A phenocopy, as general rule, is defined as: a phenotypic trait or disease that resembles the trait expressed by a particular genotype, but in an individual who is not a carrier of that genotype; an environmentally induced, nongenetic alteration of a phenotype to a form that resembles the expression of a known genetic mutation [1]. Brugada phenocopies (BrP) are clinical entities that are etiologically distinct from true congenital BrS and are characterized by type 1 or type 2 Brugada ECG
Conclusions
Brugada type 1 ECG could be an early sign of an occult structural heart disease with implications in clinical management and genetic counselling. In order to confirm (or refute) the fascinating hypothesis of an overlap between Brugada Syndrome and HCM, further research is needed.
Author statement
Patients described in the manuscript gave their consent to publication. The first patient described in this report was already included in a recently published multicenter case series from the same authors.
This paper has not been published previously and is not under consideration for publication elsewhere. Possible publication is approved by all authors and by the responsible authorities where the work has been carried out. If accepted, it will not be published elsewhere without the written
Declaration of Competing Interest
None.
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Cited by (3)
Brugada ECG phenocopy in hypertrophic cardiomyopathy: The time matter
2023, Journal of ElectrocardiologyCitation Excerpt :Recently, two other cases of incidental findings of a Brugada ECG pattern in the context of HCM were described [3]. Both patients had common pathogenetic splicing mutations in the MYBPC3 sarcomeric gene (encoding for the cardiac myosin-binding protein C) responsible for HCM with no genetic mutations associated with Brugada syndrome [3]. This fact suggests that patients are not simultaneously affected by BrS and HCM but a clinically manifest HCM with a specific genetic background can lead to an early BrS electrical manifestation.
Brugada Syndrome: More than a Monogenic Channelopathy
2023, Biomedicines