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Annual Review of Medicine

Volume 76, 2025

RASopathies in Cardiac Disease

  • Saravanakkumar Chennappan1 and Maria Irene Kontaridis1,2,3
  • 1Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, New York, USA; email: [email protected] 2Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA 3Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
  • Vol. 76:301-314 (Volume publication date January 2025)
  • First published as a Review in Advance on November 22, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

RASopathies are a group of clinically overlapping autosomal dominant disorders caused primarily by mutations in genes that reside along the canonical Ras–mitogen-activated protein kinase signaling cascade. Though individually rare, collectively, these disorders constitute one of the largest families of congenital disorders worldwide, particularly for infantile hypertrophic cardiomyopathy. Significantly, despite almost five decades of RASopathy research, therapeutic options remain limited and focused primarily on treating symptoms rather than disease etiology. Targeting the genes causal to these disorders, and the nodal pathways critical for their regulation, however, has been challenging. In this review, we highlight these challenges, particularly with respect to congenital heart defects and cardiac diseases and discuss limitations and future directions for approaches to new therapeutic strategies.

Keyword(s): congenital heart defects, Costello syndrome, developmental disorders, hypertrophic cardiomyopathy, Noonan syndrome, RASopathies
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2025-01-27
2025-06-23
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RASopathies in Cardiac Disease
Annual Review of Medicine 76, 301 (2025); https://doi.org/10.1146/annurev-med-042823-013552
/content/journals/10.1146/annurev-med-042823-013552
/content/journals/10.1146/annurev-med-042823-013552
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