Lymphatic dysfunction, not aplasia, underlies Milroy disease.
Microcirculation
; 17(4): 281-96, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20536741
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Linfático
/
Linfedema
Tipo de estudo:
Observational_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Microcirculation
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido