To report experiences of treating infants with Noonan syndrome and lymphatic abnormalities with refractory chylous effusions using Trametinib.
Approach:
Patient cohort: Six infants with genetically confirmed Noonan syndrome and refractory lymphatic abnormalities were treated with Trametinib. Clinical assessments and MR lymphangiography were performed at baseline, 6 weeks, and 1 year.
Key Findings:
All patients showed considerable clinical improvement after one year of Trametinib therapy.
None of the patients required chest drainage, and no clinical signs of chylothorax were present.
Follow-up MR lymphangiography demonstrated a decrease in pleural effusions in all cases, with three patients showing no residual fluid.
Pathologic pulmonary and pleural lymphatic perfusion decreased in all cases (median 3 vs. 1).
Lymphatic imaging did not show normalization of lymphatic anatomy or flow in any patient.
Interpretation:
Trametinib therapy resulted in significant clinical improvement in infants with lymphatic abnormalities associated with Noonan syndrome, but MR lymphangiography indicated limited remodeling of the central lymphatic system.
Limitations:
Small sample size of six patients limits generalizability.
Lack of normalization of lymphatic anatomy or flow despite clinical improvement.
Conclusion:
Trametinib may be a promising treatment option for lymphatic abnormalities in Noonan syndrome, though further studies are needed to assess long-term outcomes and anatomical changes.
