Taizo A. Nakano, Alexander W. Rankin, Aparna Annam, Ann M. Kulungowski, Leslie M. McCallen, Lauren R. Hill, Kathryn C. Chatfield
University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado.
United States
Journal of Pediatrics
J Pediatr 2022; 248: 81-88
DOI: 10.1016/j.jpeds.2022.05.030
Abstract
Objective: To evaluate the effect of the RAS-MAPK pathway inhibitor trametinib on medically refractory chylous effusions in 3 hospitalized patients with Noonan syndrome.
Study design: Pharmacologic MEK1/2 inhibition has been used to treat conditions associated with Noonan syndrome, given that activation of RAS-MAPK pathway variants leads to downstream MEK activation. We describe our experience with 3 patients with Noonan syndrome (owing to variants in 3 distinct genes) and refractory chylous effusions treated successfully with MEK inhibition. A monitoring protocol was established to standardize medication dosing and monitoring of outcome measures.
Results: Subjects demonstrated improvement in lymphatic leak with additional findings of improved growth and normalization of cardiac and hematologic measurements. Trametinib was administered safely, with only moderate skin irritation in 1 subject.
Conclusions: Improvements in a variety of quantifiable measurements highlight the potential utility of MEK1/2 inhibition in patients with Noonan syndrome and life-threatening lymphatic disease. Larger, prospective studies are needed to confirm efficacy and assess long-term safety.
Category
Pulmonary Lymphatic Disease
Genetic Factors Associated with Pulmonary Vascular Disease
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes