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Emerging Genotype–Phenotype Associations in Dilated Cardiomyopathy

  • Myocardial Disease (A Abbate and M Merlo, Section Editors)
  • Published:
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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.

Summary

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.

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, 94103, USA

    Joyce N. Njoroge

  2. Stanford Center for Inherited Cardiovascular Disease, Stanford University School of Medicine, Falk CVRB room CV-154, 870 Quarry Road, Stanford, CA, 94305, USA

    Joyce N. Njoroge, Jennifer C. Mangena, Chiaka Aribeana & Victoria N. Parikh

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  1. Joyce N. Njoroge
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  4. Victoria N. Parikh
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Correspondence to Victoria N. Parikh.

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Conflict of Interest

VNP is on the SAB of and receives research support from BioMarin, Inc., and has minor consulting relationships with Viz.ai, and Constantiam Biosciences. VNP also reports support from NHLBI K08HL14318503, as well as payment for UCSD genomic medicine grand rounds. The other authors declare that they have no conflict of interest.

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Njoroge, J.N., Mangena, J.C., Aribeana, C. et al. Emerging Genotype–Phenotype Associations in Dilated Cardiomyopathy. Curr Cardiol Rep 24, 1077–1084 (2022). https://doi.org/10.1007/s11886-022-01727-z

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