title: Hydrops fetalis and pulmonary lymphangiectasia due to FOXC2 mutation: an autosomal dominant hereditary lymphedema syndrome with variable expression.
abstract: Non-immune hydrops fetalis may find its origin within genetically determined lymphedema syndromes, caused by mutations in FOXC2 and SOX-18. We describe a newborn girl, diagnosed with non-immune hydrops fetalis at a gestational age of 30 weeks. Family history revealed the presence of an autosomal dominant late-onset form of lymphedema of the lower limbs in her father, associated with an aberrant implantation of the eyelashes in some individuals. The newborn, hydropic girl suffered from severe pulmonary lymphangiectasia, resulting in terminal respiratory failure at the age of 3 months. Genetic analysis in both the father and the newborn girl demonstrated a heterozygous FOXC2 mutation, i.e., c.939C>A, p.Tyr313X. Her two older sisters are currently asymptomatic and the parents decided not to test them for the FOXC2 mutation.
  
  
  CONCLUSIONS
  Patients with a mutation in the FOXC2 transcription factor usually show lower limb lymphedema with onset at or after puberty, together with distichiasis. However, the eye manifestations can be very mild and easily overlooked. The association between FOXC2 mutation and neonatal hydrops resulting in terminal respiratory failure is not reported so far. Therefore, in sporadic patients diagnosed with non-immune hydrops fetalis, lymphangiogenic genes should be systematically screened for mutations. In addition, all cases of fetal edema must prompt a thorough analysis of the familial pedigree, in order to detect familial patterns and to facilitate adequate antenatal counseling.
authors.affiliation: University Hospital of Leuven, Herestraat 49, 3000 Leuven, Belgium. gwendolyn.debruyn@uzleuven.be
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: de Bruyn
authors.forename: Alexandra
authors.initials: A
authors.lastname: Casaer
authors.forename: Katrien
authors.initials: K
authors.lastname: Devolder
authors.forename: Geert
authors.initials: G
authors.lastname: Van Acker
authors.forename: Hilde
authors.initials: H
authors.lastname: Logghe
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Luc
authors.initials: L
authors.lastname: Cornette
mesh_terms: D018389:Codon, Nonsense; D017809:Fatal Outcome; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005799:Genes, Dominant; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D015160:Hydrops Fetalis / Q000175:diagnosis / Q000235:genetics*; D007231:Infant, Newborn; D008171:Lung Diseases / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D008200:Lymphangiectasis / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D008209:Lymphedema / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; C082078:mesenchyme fork head 1 protein