Emerging Genotype-Phenotype Associations in Dilated Cardiomyopathy

Abstract

Purpose of review: The disease burden of inherited dilated cardiomyopathy (DCM) is large and likely underestimated. This population stands to benefit immensely from therapeutic approaches tailored to the underlying genetic causes. Here, we review recent advances in understanding novel genotype-phenotype relationships and how these can improve the care of patients with inherited DCM.

Recent findings: In the last several years, discovery of novel DCM-associated genes, gene-specific DCM outcomes, and nuanced information about variant-environment interactions have advanced our understanding of inherited DCM. Specifically, novel associations of genes with specific clinical phenotypes can help to assess sudden cardiac death risk and guide counseling around behavioral and environmental exposures that may worsen disease. Important expansions of the current genotype-phenotype profiling include the newly DCM-associated FLNC variant, prognostically significant LMNA, DSP inflammatory cardiomyopathy, and the highly penetrant features of RBM20 variants as well as the role of TTN variants in compounding the effects of environmental factors on toxin-mediated DCM. Future directions to improve diagnostic accuracy and prognostic improvement in DCM will center not just on identification of new genes, but also on understanding the interaction of known and novel variants in known DCM genes with patient genetic background and environment.

Keywords: Dilated cardiomyopathy; Genetic disease; Inherited cardiomyopathy; Population genomics; Precision medicine.