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Milroy disease and the VEGFR-3 mutation phenotype
1SW Thames Regional Genetics Unit, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. gbrice@sghms.ac.uk
Journal of Medical Genetics
|February 4, 2005
Summary
Primary congenital lymphoedema, also known as Milroy disease, is linked to vascular endothelial growth factor receptor 3 (VEGFR-3) gene mutations. Most patients exhibit lower limb oedema from birth, with other symptoms like cellulitis and hydrocoele also observed.
Area of Science:
- Genetics
- Vascular Biology
- Pediatric Medicine
Background:
- Primary congenital lymphoedema (Milroy disease) is a rare autosomal dominant disorder.
- Recent research identified mutations in the vascular endothelial growth factor receptor 3 (VEGFR-3) gene as a major cause.
- VEGFR-3 gene mutations have been reported in 13 families globally.
Purpose of the Study:
- To review primary congenital lymphoedema (Milroy disease) based on clinical findings.
- To analyze the clinical manifestations in individuals with VEGFR-3 mutations.
- To establish the correlation between VEGFR-3 mutations and clinical phenotype.
Main Methods:
- Review of clinical data from 71 subjects across 10 families.
- Genetic analysis confirming VEGFR-3 mutations in all studied individuals.
- Detailed clinical examination to identify associated signs and symptoms.
Main Results:
- All 71 subjects possessed a VEGFR-3 mutation.
- Ninety percent of subjects presented with lower limb oedema, typically from birth.
- Additional findings included cellulitis (20%), large calibre leg veins (23%), papillomatosis (10%), upslanting toenails (10%), and hydrocoele in males (37%).
Conclusions:
- Clinical examination reveals limited signs beyond lower limb oedema in Milroy disease.
- Rigorous phenotyping of patients with suspected Milroy disease yields a high rate of VEGFR-3 mutation detection.
- VEGFR-3 mutations are strongly associated with primary congenital lymphoedema.