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Lymphatic dysfunction, not aplasia, underlies Milroy disease.
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2010 (English)In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 17, no 4Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Milroy disease is an inherited autosomal dominant lymphoedema caused by mutations in the gene for vascular endothelial growth factor receptor-3 (VEGFR-3, also known as FLT4). The phenotype has to date been ascribed to lymphatic aplasia. We further investigated the structural and functional defects underlying the phenotype in humans.

METHODS: The skin of the swollen foot and the non-swollen forearm was examined by (i) fluorescence microlymphangiography, to quantify functional initial lymphatic density in vivo; and (ii) podoplanin and LYVE-1 immunohistochemistry of biopsies, to quantify structural lymphatic density. Leg vein function was assessed by colour Doppler duplex ultrasound.

RESULTS: Milroy patients exhibited profound (86-91%) functional failure of the initial lymphatics in the foot; the forearm was unimpaired. Dermal lymphatics were present in biopsies but density was reduced by 51-61% (foot) and 26-33% (forearm). Saphenous venous reflux was present in 9/10 individuals with VEGFR3 mutations, including two carriers.

CONCLUSION: We propose that VEGFR3 mutations in humans cause lymphoedema through a failure of tissue protein and fluid absorption. This is due to a profound functional failure of initial lymphatics and is not explained by microlymphatic hypoplasia alone. The superficial venous valve reflux indicates the dual role of VEGFR-3 in lymphatic and venous development.

Place, publisher, year, edition, pages
2010. Vol. 17, no 4
National Category
Basic Medicine
URN: urn:nbn:se:uu:diva-287152DOI: 10.1111/j.1549-8719.2010.00030.xPubMedID: 20536741OAI: oai:DiVA.org:uu-287152DiVA: diva2:922261
Available from: 2016-04-22 Created: 2016-04-22 Last updated: 2016-04-22

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