A homozygous variant in growth and differentiation factor 2 (GDF2) may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis

Am J Med Genet A. 2020 Sep;182(9):2152-2160. doi: 10.1002/ajmg.a.61743. Epub 2020 Jul 2.

Abstract

The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. A genetic cause seemed plausible as the maternal history revealed a fatal nonimmune hydrops fetalis. A homozygous truncating variant in GDF2 (c.451C>T, p.(Arg151*)) was detected with exome sequencing. Genetic analysis of tissue obtained from the deceased fetal sibling revealed the same homozygous variant. The parents and two healthy siblings were heterozygous for the GDF2 variant. Skin and lung biopsies in the index patient, as well as the revised lung biopsy of the deceased fetal sibling, showed lymphatic dysplasia and lymphangiectasia. To the best of our knowledge, this is the first report of an association between a homozygous variant in GDF2 with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis.

Keywords: BMP9; GDF2; hereditary hemorrhagic telangiectasia; lymphatic dysplasia; nonimmune hydrops fetalis; pulmonary arterial hypertension.

Publication types

  • Case Reports

MeSH terms

  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • Exome Sequencing
  • Female
  • Growth Differentiation Factor 2 / genetics*
  • Homozygote
  • Humans
  • Hydrops Fetalis / diagnosis
  • Hydrops Fetalis / genetics*
  • Hydrops Fetalis / pathology
  • Infant, Newborn
  • Lymphangiectasis, Intestinal / diagnosis
  • Lymphangiectasis, Intestinal / genetics*
  • Lymphangiectasis, Intestinal / pathology
  • Lymphedema / diagnosis
  • Lymphedema / genetics*
  • Lymphedema / pathology
  • Polyhydramnios / diagnosis
  • Polyhydramnios / genetics*
  • Polyhydramnios / pathology
  • Pregnancy
  • Thoracentesis
  • Ultrasonography, Prenatal

Substances

  • GDF2 protein, human
  • Growth Differentiation Factor 2

Supplementary concepts

  • Hennekam lymphangiectasia lymphedema syndrome