Sporadic in utero generalized edema caused by mutations in the lymphangiogenic genes VEGFR3 and FOXC2.
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.
Ghalamkarpour
Arash
A
Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Debauche
Christian
C
Haan
Eric
E
Van Regemorter
Nicole
N
Sznajer
Yves
Y
Thomas
Dominique
D
Revencu
Nicole
N
Gillerot
Yves
Y
Boon
Laurence M
LM
Vikkula
Miikka
M
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*
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