Genotype-Phenotype Correlation in Familial BAG3 Mutation Dilated Cardiomyopathy

Abstract

We report the case of a 22-year-old male who visited a cardiologist after the first episode of atrial fibrillation (AF). Echocardiography and magnetic resonance imaging revealed decreased left ventricular (LV) systolic function with dilated LV. An intermittent second-degree AV (atrioventricular) block was detected during 24 h Holter monitoring. Genetic test revealed the pathogenic variant of the BAG3 (BLC2-associated athanogene 3) gene. Due to the high risk of heart failure (HF) progression and ventricular arrhythmias, an event recorder was implanted and a pathogenetic HF treatment was prescribed. The analysis of genealogy revealed that the patient's father, at the age of 32, was diagnosed with dilated cardiomyopathy (DCM) and recurrent AF episodes. Genetic testing also confirmed a pathogenic variant of the BAG3 gene. Currently, with the optimal treatment of HF, the patient's disease has been stable for three years and the condition is closely monitored on an outpatient basis. So, we demonstrate the importance of early detection for genetic testing and the unusual stability exhibited by the patient's optimal medical therapy for 3 years.

Keywords: BAG3; dilated cardiomyopathy; heart failure; inherited cardiomyopathies.

Figure 1

(a) ECG–without significant changes; (b) ECG–an intermittent second-degree AV block.

Figure 2

Left ventricular global longitudinal strain by speckle-tracking echocardiography.

Figure 3

Cardiac magnetic resonance imaging with decreased LV systolic function and dilated LV.

Figure 4

The patient’s genealogy scheme. The patient’s father started having heart insufficiency symptoms at 30 years of age. The grandfather from father’s side and his sisters died of heart disorder about 60 years of age, and the grandfather’s brother at 40 years of age. It is noted that grandfather’s sister started having arrhythmias at a younger age. The great-grandmother also died from a heart disorder. No relevant information from the patient’s mother’s side. Genetic testing was offered to the patient’s father’s brother and his cousins.