title: Sporadic in utero generalized edema caused by mutations in the lymphangiogenic genes VEGFR3 and FOXC2.
abstract: OBJECTIVE
  To investigate the genetic causes of idiopathic sporadic prenatal generalized edema.
  
  
  METHODS
  In a series of 12 patients, in whom in utero generalized skin edema or hydrops fetalis had been diagnosed, we screened 3 lymphangiogenic genes, VEGFR3, FOXC2, and SOX18.
  
  
  RESULTS
  In 3 of the patients, we identified a mutation: 2 in VEGFR3 and 1 in FOXC2. Two of the mutations were de novo and one was either de novo or nonpenetrant inherited. In these patients, the generalized edema resorbed spontaneously, either in utero or after birth. In the 2 individuals with a VEGFR3 mutation, edema remained limited to lower limbs.
  
  
  CONCLUSIONS
  Mutations in the VEGFR3 and FOXC2 genes account for a subset of patients with unexplained in utero generalized subcutaneous edema and hydrops fetalis without family history of lymphedema. Lymphangiogenic genes should be screened for mutations in sporadic patients diagnosed with fetal edema.
authors.affiliation: Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Arash
authors.initials: A
authors.lastname: Ghalamkarpour
authors.forename: Christian
authors.initials: C
authors.lastname: Debauche
authors.forename: Eric
authors.initials: E
authors.lastname: Haan
authors.forename: Nicole
authors.initials: N
authors.lastname: Van Regemorter
authors.forename: Yves
authors.initials: Y
authors.lastname: Sznajer
authors.forename: Dominique
authors.initials: D
authors.lastname: Thomas
authors.forename: Nicole
authors.initials: N
authors.lastname: Revencu
authors.forename: Yves
authors.initials: Y
authors.lastname: Gillerot
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Boon
authors.forename: Miikka
authors.initials: M
authors.lastname: Vikkula
mesh_terms: D000328:Adult; D002648:Child; D018389:Codon, Nonsense; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D015160:Hydrops Fetalis / Q000235:genetics*; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D011247:Pregnancy; D055760:SOXF Transcription Factors / Q000235:genetics; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D051858:Forkhead Transcription Factors; C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; C082078:mesenchyme fork head 1 protein; D040321:Vascular Endothelial Growth Factor Receptor-3