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Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition

Gordon, K; Moore, M; Van Zanten, M; Pearce, J; Itkin, M; Madden, B; Ratnam, L; Mortimer, PS; Nagaraja, R; Mansour, S (2022) Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition. Frontiers in Genetics, 13. p. 1001105. ISSN 1664-8021 https://doi.org/10.3389/fgene.2022.1001105
SGUL Authors: Mansour, Sahar

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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.

Item Type: Article
Additional Information: Copyright © 2022 Gordon, Moore, Van Zanten, Pearce, Itkin, Madden, Ratnam, Mortimer, Nagaraja and Mansour. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: 0604 Genetics, 1103 Clinical Sciences, 1801 Law
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Frontiers in Genetics
ISSN: 1664-8021
Dates:
DateEvent
27 September 2022Published
7 September 2022Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
MR/P011543/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
CRSII5_177191/1Fonds National Suisse de la Recherche ScientifiqueUNSPECIFIED
URI: https://openaccess.sgul.ac.uk/id/eprint/114876
Publisher's version: https://doi.org/10.3389/fgene.2022.1001105

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