Familial Dilated Cardiomyopathy and Sudden Cardiac Arrest: New Association with a SCN5A Mutation

Abstract

Dilated cardiomyopathy (DCM) has significant morbidity and mortality. Familial transmission is reported in 20-35% of cases, highlighting the role of genetics in this disorder. We present an interesting family in which the index case is a 64-year-old woman who survived a sudden cardiac arrest. She presented left ventricular dilatation and dysfunction, which indicated the presence of DCM, as well as a history of DCM and sudden arrest in her family (mother and sister). Genetic testing identified a heterozygous mutation c.74A > G missense change that causes an amino acid, p.Glu25Gly, change in the N-terminal domain of the SCN5A protein. After performing an exhaustive family medical history, we found that this previously not described mutation segregated within the family. All relatives with the DCM phenotype were carriers, whereas none of the noncarriers showed signs of heart disease, so this mutation is the most likely cause of the disease. This is the first time that a variant in the N-terminal domain of SCN5A has been associated with DCM.

Keywords: SCN5A; dilated cardiomyopathy; familial dilated cardiomyopathy; genetic study; novel mutation.

Figure 1

Pedigree of the affected family displaying the segregation of c.74A > G with cardiopathies.

Figure 2

Magnetic resonance image (MRI) of the proband. The arrow shows intramyocardial late gadolinium enhancement (LGE) located in the inferoseptal wall.

Figure 3

Variants in cardiac Na_v 1.5 voltage-gated sodium channel (SCN5A) reported previously in association with dilated cardiomyopathy (colored in red). Colored in yellow is the p.Glu25Gly variant described in this article. Two additional variants, c.2550-2551insTG and c.3318dupC, causing truncation of the encoded protein in patients with dilated cardiomyopathy, are not shown. This figure is an adaptation of Asatryan (2019) [12].