Milroy disease and the VEGFR-3 mutation phenotype

J Med Genet. 2005 Feb;42(2):98-102. doi: 10.1136/jmg.2004.024802.


Primary congenital lymphoedema (Milroy disease) is a rare autosomal dominant condition for which a major causative gene defect has recently been determined. Mutations in the vascular endothelial growth factor receptor 3 (VEGFR-3) gene have now been described in 13 families world-wide. This is a review of the condition based on the clinical findings in 71 subjects from 10 families. All 71 individuals have a mutation in VEGFR-3. Ninety per cent of the 71 individuals carrying a VEGFR-3 mutation showed signs of oedema, which was confined in all cases to the lower limbs. In all but two cases onset of swelling was from birth. Other symptoms and signs included cellulitis (20%), large calibre leg veins (23%), papillomatosis (10%), and upslanting toenails (10%). In males, hydrocoele was the next most common finding after oedema (37%). Thorough clinical examination of these patients indicates that there are few clinical signs in addition to lower limb oedema. Rigorous phenotyping of patients produces a high yield of VEGFR-3 mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adult
  • Age of Onset
  • Female
  • Genetic Carrier Screening
  • Humans
  • Lymphedema / diagnosis*
  • Lymphedema / epidemiology
  • Lymphedema / genetics
  • Male
  • Mutation*
  • Nails, Malformed
  • Papilloma / pathology
  • Phenotype
  • Saphenous Vein / pathology
  • Urogenital Abnormalities / diagnosis
  • Varicose Veins / diagnosis
  • Vascular Endothelial Growth Factor Receptor-3 / genetics*


  • Vascular Endothelial Growth Factor Receptor-3