Department of Clinical Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands.
Am J Med Genet A. 2020 Sep;182(9):2152-2160. doi: 10.1002/ajmg.a.61743. Epub 2020 Jul 2.
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.
非免疫性胎儿水肿的病因广泛，包括遗传疾病。我们描述了一例足月出生的女性新生儿，其患有晚期广泛的非免疫性胎儿水肿，即羊水过多、水肿和先天性双侧乳糜胸。该新生儿通过重复胸腔穿刺术、全胃肠外营养、奥曲肽静脉内注射以及最终的胸膜固定术和皮质类固醇治疗成功治愈。遗传原因似乎是合理的，因为母亲的病史显示出致命的非免疫性胎儿水肿。通过外显子组测序检测到 GDF2 中的纯合截短变异(c.451C>T，p.(Arg151*))。对已故胎儿同胞组织进行的基因分析显示出相同的纯合变异。父母和两个健康的兄弟姐妹为 GDF2 变异的杂合子。该患者的皮肤和肺活检，以及已故胎儿同胞的修订肺活检，显示出淋巴管发育不良和淋巴管扩张。据我们所知，这是首例 GDF2 中的纯合变异与淋巴管发育不良、胸腔积液和非免疫性胎儿水肿相关的报道。
