Sporadic In Utero Generalized Edema Caused by Mutations in the Lymphangiogenic Genes VEGFR3 and FOXC2.
J Pediatr. 2009 Apr 23
Ghalamkarpour A, Debauche C, Haan E, Van Regemorter N, Sznajer Y, Thomas D, Revencu N, Gillerot Y, Boon LM, Vikkula M.
Laboratory of Human Molecular Genetics (A.G., N.R., L.B., M.V.), de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; Department of Neonatology (C.D.), Cliniques Universitaires Saint-Luc, Brussels, Belgium; Department of Genetic Medicine (E.H.), Women's and Children's Hospital, North Adelaide, Australia, and Department of Paediatrics, University of Adelaide, Adelaide, Australia; Centre de Génétique ULB (N.V., Y.S.), Hôpital Erasme, Brussels, Belgium; Unité de Génétique Clinique Pédiatrique (Y.S.), Université Libre de Bruxelles, Brussels, Belgium; Unité Diagnostic Anténatal, Hôpitaux Iris Sud (D.T.), Brussels, Belgium; Center for Human Genetics (Y.G.), Cliniques Universitaires Saint-Luc, Brussels, Belgium; and Centre for Vascular Anomalies (L.B.), Cliniques Universitaires Saint-Luc, Brussels, Belgium.
OBJECTIVES: To investigate the genetic causes of idiopathic sporadic prenatal generalized edema.
STUDY DESIGN: 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.