Successful treatment of refractory chylothorax with MEK inhibitor trametinib in a child with Noonan syndrome: case report

Abstract

Background Refractory chylous effusions due to lymphatic dysplasia related to Noonan syndrome cause significant morbidity and mortality due to protein and immunoglobulin losses. Very few cases have been published reporting successful treatment of patients with trametinib where all conventional treatments had failed. Case Summary We present a girl with Noonan syndrome and hypertrophic cardiomyopathy who presented with life threatening refractory chylothorax where all conventional treatment options failed. She was successfully treated with mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib. Discussion MEK inhibition with trametinib is emerging as a possible salvage treatment option for a subset of patients with Noonan syndrome and severe pulmonary lymphangiectasia. More experience is required to establish optimal treatment regimen and long term outcomes.

Noonan Syndrome and its Ophthalmic Implications: Insights from a Pediatric Case

“…7 NS is linked to serious cardiac abnormalities, specifically intractable cyothorax and hypertrophic cardiomyopathy, which can ultimately result in mortality. 8 Furthermore, it has been recorded that NS is linked to renal problems, and a young patient with NS suffered an awful outcome following a kidney transplantation. 9 Early oph- thalmological evaluation is crucial in NS due to the potential accompanying pathologies that can cause vision loss.…”

A case report of myelodysplastic syndrome in a patient with PTPN11‐related Noonan syndrome

“…Due to thrombocytopenia and anemia, a bone marrow biopsy was performed, which showed hypocellularity without concern for dysplasia or cytogenetic abnormalities. She was started on trametinib for the chylothorax at 1 month of age based on studies showing response in patients with Noonan syndrome, 4,5 with improvement in respiratory symptoms, weaning respiratory support, and removal of chest tubes. She subsequently developed progressive cytopenia, thought to be a side effect of trametinib, so this was discontinued (see Table 1 for clinical course, counts, and bone marrow results).…”

Central conducting lymphatic anomaly: from bench to bedside

“…In an adult with RIT1 –Noonan syndrome and lymphatic failure, trametinib therapy resulted in increased albumin level, resolution of ascites in 3 months, and reduction of pericardial effusion within 18 months ( 84 ). Similarly, in a child with RIT1 –Noonan syndrome who had chylous pleural effusions drained at the initiation of a 3-month course of trametinib, the effusions did not recur ( 141 ). In another case series, three infants with Noonan syndrome ( SOS1 , RIT1 , PTPN11 ) all had a reduction in chylous effusions, chylous ascites, and improvement in respiratory status with trametinib therapy ( 86 ).…”