Trametinib for Refractory Chylous Effusions and Systemic Complications in Children with Noonan Syndrome.

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.
(Published by Elsevier Inc.)