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Milroy disease and the VEGFR-3 mutation phenotype
  1. G Brice1,
  2. A H Child2,
  3. A Evans2,
  4. R Bell1,
  5. S Mansour1,
  6. K Burnand3,
  7. M Sarfarazi4,
  8. S Jeffery1,
  9. P Mortimer5
  1. 1SW Thames Regional Genetics Unit, St George’s Hospital Medical School, London, UK
  2. 2Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK
  3. 3Department of Academic Surgery, St Thomas Hospital, London, UK
  4. 4Molecular Ophthalmic Genetics Laboratory, University of Connecticut Health Center, Farmington, CT, USA
  5. 5Department of Cardiac and Vascular Sciences (Dermatology), St George’s Hospital Medical School, London, UK
  1. Correspondence to:
 Glen Brice
 SW Thames Regional Genetics Unit, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK;


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.

  • VEGFR-3, vascular endothelial growth factor receptor 3
  • hydrocoele
  • lymphoedema
  • Milroy disease
  • VEGFR-3

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  • RB and GB were supported by the British Heart Foundation. AHC was supported by the Bluff Field Charitable Trust. MS was supported by National Heart, Lung and Blood Institute, Grant #: R01-HL66150.

  • Conflict of interest: none declared.

  • This study had the approval of the Wandsworth Local Research Ethics Committee and the University of Connecticut Health Center Institutional Review Board. Written consent was obtained from all participants or, in the case of a child, from their parent.