Sporadic In Utero Generalized Edema Caused by Mutations in the Lymphangiogenic Genes VEGFR3 and FOXC2.

[lymphedemapeople]

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.

Elsevier ScienceDirect

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