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

Aukema, S. M., ten Brinke, G. A., Timens, W., Vos, Y. J., Accord, R. E., Kraft, K. E., Santing, M. J., Morssink, L. P., Streefland, E., van Diemen, C. C., Vrijlandt, E. J. L. E., Hulzebos, C. & Kerstjens-Frederikse, W. S., 2-Jul-2020, In : American Journal of Medical Genetics. Part A. 182, 9, p. 2152-2160 9 p.

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

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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 inGDF2(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 theGDF2variant. 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 inGDF2with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis.

Original languageEnglish
Pages (from-to)2152-2160
Number of pages9
JournalAmerican Journal of Medical Genetics. Part A
Issue number9
Publication statusPublished - 2-Jul-2020


  • BMP9, GDF2, hereditary hemorrhagic telangiectasia, lymphatic dysplasia, nonimmune hydrops fetalis, pulmonary arterial hypertension, PULMONARY INTERSTITIAL GLYCOGENOSIS, PROTEIN 9, KINASE 1, MUTATIONS, PHENOTYPE, TRISOMY-20, KNOWLEDGE, SPECTRUM, INSIGHTS

ID: 129090034