Case Report: Comprehensive evaluation of ECG phenotypes and genotypes in a family with Brugada syndrome carrying SCN5A-R376H

Abstract

Background: Brugada syndrome (BrS) is a channelopathy that can lead to sudden cardiac death in the absence of structural heart disease. Patients with BrS can be asymptomatic or present with symptoms secondary to polymorphic ventricular tachycardia or ventricular fibrillation. Even though BrS can exhibit autosomal dominant inheritance, it is not easy to identify the phenotype and genotype in a family thoroughly.

Case: We report the case of a 20-year-old man with variants in SCN5A and RyR2 genes who was resuscitated from sudden cardiac death during sleep due to a ventricular fibrillation. The patient did not have underlying diseases. The routine laboratory results, imaging study, coronary angiogram, and echocardiogram (ECG) were normal. A type 1 BrS pattern was identified in one resting ECG. Furthermore, prominent J wave accentuation with PR interval prolongation was identified during therapeutic hypothermia. Therefore, we were easily able to diagnose BrS. For secondary prevention, the patient underwent implantable cardioverter defibrillator implantation. Before discharge, a genetic study was performed using next-generation sequencing. Genotyping was performed in the first-degree relatives, and ECG evaluations of almost all maternal and paternal family members were conducted. The proband and his mother showed SCN5A-R376H and RyR2-D4038Y variants. However, his mother did not show the BrS phenotype on an ECG. One maternal aunt and uncle showed BrS phenotypes.

Conclusion: Genetics alone cannotdiagnose BrS. However, genetics could supply evidence or direction for evaluating ECG phenotypes in family groups. This case report shows how family evaluation using ECGs along with a genetic study can be used in BrS diagnosis.

Keywords: Brugada syndrome; SCN5A; family screening; genetic study; sudden cardiac death.

Figure 1

The initial ECG of the index patient, which was recorded on an automated external defibrillator. Defibrillation was performed for the ventricular fibrillation that occurred during transfer of the patient to the emergency room (A). After the cardioversion, ST elevation was observed in the defibrillator-patch ECG (B). The initial 12-lead ECG showed normal sinus rhythms with first-degree AV block (C). The PR interval was 240 ms. A type 2 Brugada pattern ECG was observed in V1 and V2. The V1 and V2 showed dynamic changes that is more like type 1 ECG (D). ECG, electrocardiogram.

Figure 2

ECG of the index patient during and after therapeutic hypothermia. Widespread J wave accentuation was observed during the hypothermia (A). Marked PR-interval prolongation (440 ms) was identified after therapeutic hypothermia (B). In a follow-up ECG, a spontaneous type 1 Brugada pattern was identified with an incidental atrial fibrillation (C). ECG, electrocardiogram.

Figure 3

An implantable cardioverter defibrillator shock during sleep was detected and terminated successfully.

Figure 4

Family pedigree with ECG phenotypes in V1 and V2. The proband's ECG showed a type 1 Brugada pattern in V1. The brother's ECG showed a long PR interval of 480 ms and incomplete RBBB in the 3rd intercostal V1 and V2. The father's ECG showed a long PR interval of 240 ms. The mother's ECG showed a long PR interval of 220 ms without the Brugada pattern on the ECG. One maternal aunt showed a type 1 Brugada pattern in V2. One maternal uncle, who experienced aborted sudden cardiac death, showed a suspicious BrS-pattern on the ECG in V1. One paternal aunt showed an RBBB with a normal PR interval. One paternal female cousin showed a type 2 Brugada pattern with a PR interval of 200 ms in V2. Information about the genetic mutations of first-degree relatives of the patient is also given. The squares represent males, and the circles represent females. The squares/circles with black in the left upper quadrant represent the BrS-like ECG. The squares/circles with black in the left lower quadrant represent PR prolongation. The squares/circles with red in the right upper quadrant represent the SCN5A-R376H variant. The squares/circles with red in the right lower quadrant represent the DSP-Y1101C variant. 3ICS, third intercostal space; ECG, electrocardiogram; BrS, Brugada syndrome.