Introduction: Noonan syndrome is a RASopathy characterized by congenital heart defects, short stature, and lymphatic anomalies due to mutations affecting the RAS-MAPK pathway, most commonly PTPN11. Lymphatic complications such as chylous effusions pose significant management challenges, particularly in centers without advanced imaging or interventional resources. We report a case of refractory postoperative chylous effusions successfully treated with trametinib, a MEK inhibitor, in an infant with Noonan syndrome.
Description: An 8-month-old male with Noonan syndrome (PTPN11 mutation) underwent surgical repair for ASD and pulmonary stenosis. Postoperatively, he developed persistent pleural effusions confirmed to be chylous. Despite maximal medical therapy—including diuretics, elemental diet, octreotide, and parenteral nutrition—the effusions persisted. Lack of access to advanced lymphatic imaging limited anatomical assessment. Following multidisciplinary discussion and family consent, trametinib was initiated on POD 30 and titrated based on tolerance. Chest tube output gradually declined, allowing for discontinuation of octreotide, reinitiation of enteral feeds, and eventual chest tube removal. No recurrence was observed after resuming a full-fat diet. Trametinib was discontinued after 7 weeks.
Discussion: Trametinib targets the dysregulated RAS-MAPK pathway underlying lymphatic abnormalities in Noonan syndrome. In this case, resolution followed trametinib titration after failure of standard interventions, suggesting therapeutic benefit. While causality cannot be confirmed in a single case, the temporal relationship and sustained response support its role. Additionally, the ability to reintroduce full-fat feeds without recurrence strengthens its clinical relevance. However, trametinib remains off-label in this context, with limited safety data in infants and potential adverse effects requiring close monitoring. Limitations include lack of standardized dosing, feeding protocols, and access to lymphatic imaging. This case illustrates how genetic insights can guide treatment in resource-limited settings and supports further study of targeted therapies for RASopathies. Artificial intelligence assistance was used for grammar revision and rewording. All content was reviewed and approved by the authors.
