Costello syndrome: Clinical phenotype, genotype, and management guidelines

Karen W. Gripp, Lindsey A. Morse, Marni Axelrad, Kathryn C. Chatfield, Aaron Chidekel, William Dobyns, Daniel Doyle, Bronwyn Kerr, Angela E. Lin, David D. Schwartz, Barbara J. Sibbles, Dawn Siegel, Suma P. Shankar, David A. Stevenson, Mihir M. Thacker, K. Nicole Weaver, Sue M. White, Katherine A. Rauen

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence-based guidelines due to the lack of data for this rare condition.

Original languageEnglish (US)
Pages (from-to)1725-1744
Number of pages20
JournalAmerican Journal of Medical Genetics, Part A
Issue number9
StatePublished - Sep 2019
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank the families and the past NIH supported RASopathy scientific meetings that led to interaction between the clinicians, families and researchers. In addition, the authors are grateful to the Costello Syndrome Family Network for their enthusiastic support, assistance, and thoughtful comments in the development of these guidelines. This work was partially support by the National Institute of Arthritis and Musculoskeletal and Skin Diseases R01AR062165 (K.A.R.) and the Children's Miracle Network (S.P.S.).

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.


  • Costello syndrome
  • HRAS mutation
  • RASopathy
  • management guidelines


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