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Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including
Kristiana Gordon1,2, Matthew Moore3, Malou Van Zanten1
1Lymphovascular Research Unit, Molecular and Clinical Sciences Research Institute, University of London, London, United Kingdom.
Abstract:
The RASopathies are a group of genetic conditions resulting from mutations within the RAS/mitogen-activated protein kinase (RAS-MAPK) pathway. Lymphatic abnormalities are commonly associated with these conditions, however central conducting lymphatic abnormalities (CCLA) have only recently been described. CCLAs may be progressive and can result in devastating systemic sequelae, such as recurrent chylothoraces, chylopericardium and chylous ascites which can cause significant morbidity and even mortality. Improvements in imaging modalities of the central lymphatics have enhanced our understanding of these complex abnormalities. Management is challenging and have mainly consisted of diuretics and invasive mechanical drainages. We describe two adult males with Noonan syndrome with a severe and progressive CCLA. In one patient we report the therapeutic role of targeted molecular therapy with the MEK inhibitor 'Trametinib', which has resulted in dramatic, and sustained, clinical improvement. The successful use of MEK inhibition highlights the importance of understanding the molecular cause of lymphatic abnormalities and utilising targeted therapies to improve quality of life and potentially life expectancy.
Insights
RASopathies, genetic disorders of the RAS-MAPK pathway, can cause severe lymphatic abnormalities. MEK inhibitor therapy showed significant improvement in a patient with Noonan syndrome and central conducting lymphatic abnormalities.
Area of Science:
- Genetics
- Molecular Biology
- Cardiology
Background:
- RASopathies are genetic disorders stemming from RAS-MAPK pathway mutations.
- Lymphatic abnormalities are common in RASopathies, with central conducting lymphatic abnormalities (CCLA) being a recent discovery.
- CCLA can lead to severe systemic complications like chylothorax, chylopericardium, and chylous ascites.
Observation:
- Two adult males with Noonan syndrome presented with severe, progressive CCLA.
- Advanced imaging improved the understanding of these central lymphatic abnormalities.
- Current management relies on diuretics and invasive drainage, often with limited success.
Findings:
- Targeted molecular therapy using the MEK inhibitor 'Trametinib' was administered to one patient.
- Trametinib resulted in dramatic and sustained clinical improvement for the patient's CCLA.
- This highlights the efficacy of targeted therapy for CCLA in RASopathies.
Implications:
- Understanding the molecular basis of lymphatic abnormalities is crucial for effective treatment.
- Targeted therapies, like MEK inhibitors, offer a promising approach to improve patient outcomes.
- This strategy may enhance quality of life and potentially increase life expectancy for individuals with RASopathies and CCLA.
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