Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition
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 desc...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1001105/full |
| _version_ | 1798021978436665344 |
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| author | Kristiana Gordon Kristiana Gordon Matthew Moore Malou Van Zanten Julian Pearce Maxim Itkin Brendan Madden Lakshmi Ratnam Peter S. Mortimer Peter S. Mortimer Rani Nagaraja Sahar Mansour Sahar Mansour |
| author_facet | Kristiana Gordon Kristiana Gordon Matthew Moore Malou Van Zanten Julian Pearce Maxim Itkin Brendan Madden Lakshmi Ratnam Peter S. Mortimer Peter S. Mortimer Rani Nagaraja Sahar Mansour Sahar Mansour |
| author_sort | Kristiana Gordon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T17:22:16Z |
| format | Article |
| id | doaj.art-53a4317ede384ad98e7ac6320078b63e |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T17:22:16Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-53a4317ede384ad98e7ac6320078b63e2022-12-22T04:12:28ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.10011051001105Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibitionKristiana Gordon0Kristiana Gordon1Matthew Moore2Malou Van Zanten3Julian Pearce4Maxim Itkin5Brendan Madden6Lakshmi Ratnam7Peter S. Mortimer8Peter S. Mortimer9Rani Nagaraja10Sahar Mansour11Sahar Mansour12Lymphovascular Research Unit, Molecular and Clinical Sciences Research Institute, University of London, London, United KingdomLymphovascular Clinic, St. George’s University Hospitals NHS Foundation Trust, London, United KingdomCardiovascular Department, St. George’s University Hospitals NHS Foundation Trust, London, United KingdomLymphovascular Research Unit, Molecular and Clinical Sciences Research Institute, University of London, London, United KingdomLymphovascular Clinic, St. George’s University Hospitals NHS Foundation Trust, London, United KingdomDivision of Interventional Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, United StatesCardiovascular Department, St. George’s University Hospitals NHS Foundation Trust, London, United KingdomDepartment of Interventional Radiology, St. George’s University Hospitals NHS Foundation Trust, London, United KingdomLymphovascular Research Unit, Molecular and Clinical Sciences Research Institute, University of London, London, United KingdomLymphovascular Clinic, St. George’s University Hospitals NHS Foundation Trust, London, United KingdomGastroenterology Department, St. George’s University Hospitals NHS Foundation Trust, London, United KingdomLymphovascular Research Unit, Molecular and Clinical Sciences Research Institute, University of London, London, United KingdomSW Thames Regional Genetics Service, St. George’s University Hospitals NHS Foundation Trust, London, United KingdomThe 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.1001105/fullchylouslymphoedemachylothoraxchylopericardiumnoonan syndromelymphedema |
| spellingShingle | Kristiana Gordon Kristiana Gordon Matthew Moore Malou Van Zanten Julian Pearce Maxim Itkin Brendan Madden Lakshmi Ratnam Peter S. Mortimer Peter S. Mortimer Rani Nagaraja Sahar Mansour Sahar Mansour Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition Frontiers in Genetics chylous lymphoedema chylothorax chylopericardium noonan syndrome lymphedema |
| title | Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition |
| title_full | Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition |
| title_fullStr | Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition |
| title_full_unstemmed | Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition |
| title_short | Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition |
| title_sort | case report progressive central conducting lymphatic abnormalities in the rasopathies two case reports including successful treatment by mek inhibition |
| topic | chylous lymphoedema chylothorax chylopericardium noonan syndrome lymphedema |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1001105/full |
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