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Advances in genetic testing have made it possible to obtain a molecular diagnosis in many fetuses with CDH. Here, we review the aneuploidies, copy number variants (CNVs), and single genes that have been clearly associated with CDH. We suggest that array\u2010based CNV analysis, with or without a chromosome analysis, is the optimal test for identifying chromosomal abnormalities and CNVs in fetuses with CDH. To identify causative sequence variants, whole exome sequencing (WES) is the most comprehensive strategy currently available. Whole genome sequencing (WGS) with CNV analysis has the potential to become the most efficient and effective means of identifying an underlying diagnosis but is not yet routinely available for prenatal diagnosis. We describe how to overcome and address the diagnostic and clinical uncertainty that may remain after genetic testing, and review how a molecular diagnosis may impact recurrence risk estimations, mortality rates, and the availability and outcomes of fetal therapy. We conclude that after the prenatal detection of CDH, patients should be counseled about the possible genetic causes of the CDH, and the genetic testing modalities available to them, in accordance with generally accepted guidelines for pretest counseling in the prenatal setting.<\/jats:p>","DOI":"10.1002\/pd.6099","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T08:57:07Z","timestamp":1642409827000},"page":"373-386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Underlying genetic etiologies of congenital diaphragmatic hernia"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1460-5169","authenticated-orcid":false,"given":"Daryl A.","family":"Scott","sequence":"first","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas 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