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Related Concept Videos

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Related Experiment Video

Updated: Sep 19, 2025

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RASopathies. Part I: Genetics and therapeutic considerations.

Zachary J Jaeger1, Natalia Maverakis Ramirez2, Ashley D Osborne3

  • 1Division of Dermatology, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Department of Internal Medicine, Veterans' Affairs Caribbean Healthcare System, San Juan, Puerto Rico; Department of Dermatology, University of California San Diego, San Diego, California.

Journal of the American Academy of Dermatology
|June 15, 2025
PubMed
Summary

RASopathies are genetic disorders affecting cell growth due to RAS pathway variants. Research explores germline and mosaic patterns, cancer predispositions, and potential therapeutic strategies targeting the RAS pathway.

Keywords:
CM-AVMCostelloECCLHRASKRASLEOPARDLegiusNF1NRASNoonanNoonan syndrome with multiple lentiginesRASRASopathiesRASopathySchimmelpenningcancercapillary malformation-arteriovenous malformationcardiofaciocutaneousencephalocraniocutaneous lipomatosisepidermal nevusgeneticsinhibitormalignancyneurofibromatosisnevus sebaceusoncogenephakomatosis pigmentokeratoticasebaceous nevustumor suppressor

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Area of Science:

  • Genetics
  • Cell Biology
  • Developmental Biology

Background:

  • RASopathies are developmental disorders stemming from genetic variants in RAS and related proteins.
  • These variants disrupt the critical RAS signaling pathway governing cell growth and development.
  • The RAS pathway's role in cell proliferation links RASopathies to both developmental abnormalities and cancer predisposition.

Purpose of the Study:

  • To review the genetic and biochemical basis of RASopathies.
  • To categorize RASopathies into germline and mosaic patterns.
  • To explore the intersection of RASopathies, cancer, and potential therapeutic interventions.

Main Methods:

  • Classification of RASopathies based on genetic patterns (germline vs. mosaic).
  • Review of associated syndromes within each category.
  • Analysis of the RAS pathway's role in oncogenesis and therapeutic implications.

Main Results:

  • Germline RASopathies include Noonan syndrome and Costello syndrome, among others.
  • Mosaic RASopathies encompass conditions like McCune-Albright syndrome and epidermal nevus syndrome.
  • The RAS pathway's dysregulation in RASopathies increases cancer risk, while some cancer therapies may benefit these patients.

Conclusions:

  • Understanding RAS pathway genetics is crucial for diagnosing and potentially treating RASopathies.
  • Targeting the RAS pathway presents therapeutic opportunities for both RASopathies and cancers.
  • Further research into RAS biochemistry may reveal novel pharmacological strategies.