Succesful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan Syndrome.

Abstract

Infants with Noonan Syndrome and hypertrophic cardiomyopathy have a poor prognosis and a high mortality especially when diagnosed before six months of age. As for the majority of the RASopathies, no medical treatment has been approved for Noonan Syndrome. Meanwhile, several approved agents targeting the same RAS/MAPK signaling pathway are used in cancer treatment. In this case report we describe a child with Noonan Syndrome caused by a pathogenic RIT1 variant, who developed severe early-onset hypertrophic cardiomyopathy and pulmonary valve stenosis. She received off-label treatment with the MEK-inhibitor trametinib which resulted in complete remission of the cardiac hypertrophy and a significant improvement of the pulmonary valve stenosis. Our case emphasizes the potential of existing cancer agents targeting the RAS/MAPK signaling pathway as successful treatment for RASopathy manifestations.

• Authors: Anne Leegaard, Pernille A Gregersen, Trine Ø Nielsen, Jesper V Bjerre, Mette M Handrup
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 65 Issue 11 Pg. 104630 (Nov 2022) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 36184070 (Publication Type: Case Reports)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Mitogen-Activated Protein Kinase Kinases
• ras Proteins
• RIT1 protein, human

Topics

• Child
• Female
• Humans
• Cardiomyopathy, Hypertrophic (drug therapy, genetics, pathology)
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Mutation
• Noonan Syndrome (drug therapy, genetics)
• Pulmonary Valve Stenosis
• ras Proteins (genetics)