Sietse M. Aukema, Gerdien A. ten Brinke, Wim Timens, Yvonne J. Vos, Ryan E. Accord, Karianne E. Kraft, Michiel J. Santing, Leonard P. Morssink, Esther Streefland, Cleo C. van Diemen, Elianne JLE Vrijlandt, Christian V. Hulzebos, Wilhelmina S. Kerstjens-Frederikse
University of Groningen, University Medical Center Groningen and Beatrix Children’s Hospital. Medical Center Leeuwarden.
Netherlands
American Journal of Medical Genetics A
Am J Med Genet A 2020; 182: 2152-2160
DOI: 10.1002/ajmg.a.61743
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.
Category
Pulmonary Lymphatic Disease
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
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