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In this review, we outline the known genetic etiologies of NIHF by fetal organ system affected, and provide a systematic approach to the evaluation of NIHF. Some of the underlying genetic disorders are associated with characteristic phenotypic features that may be seen on prenatal ultrasound, such as hepatomegaly with lysosomal storage disorders, hyperechoic kidneys with congenital nephrosis, or pulmonary valve stenosis with RASopathies. However, this is not always the case, and the approach to evaluation must include prenatal ultrasound findings as well as genetic testing and many other factors. Genetic testing that has been utilized for NIHF ranges from standard chromosomal microarray or karyotype to gene panels and broad approaches such as whole exome sequencing. Family and obstetric history, as well as pathology examination, can yield additional clues that are helpful in establishing a diagnosis. A systematic approach to evaluation can guide a more targeted approach to genetic evaluation, diagnosis, and management of NIHF.<\/jats:p>","DOI":"10.1002\/pd.5479","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T21:04:56Z","timestamp":1557781496000},"page":"732-750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["A system\u2010based approach to the genetic etiologies of non\u2010immune hydrops fetalis"],"prefix":"10.1002","volume":"39","author":[{"given":"Anne H.","family":"Mardy","sequence":"first","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences University of California, San Francisco  San Francisco CA US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa P.","family":"Chetty","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine, 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