The influence of genetics in congenital diaphragmatic hernia

Semin Perinatol. 2020 Feb;44(1):151169. doi: 10.1053/j.semperi.2019.07.008. Epub 2019 Aug 1.


Congenital diaphragmatic hernia (CDH) is a common birth defect that is associated with significant morbidity and mortality, especially when associated with additional congenital anomalies. Both environmental and genetic factors are thought to contribute to CDH. The genetic contributions to CDH are highly heterogeneous and incompletely defined. No one genetic cause accounts for more than 1-2% of CDH cases. In this review, we summarize the known genetic causes of CDH from chromosomal anomalies to individual genes. Both de novo and inherited variants contribute to CDH. Genes causing CDH are increasingly identified from animal models and from genomic strategies including exome and genome sequencing in humans. CDH genes are often transcription factors, genes involved in cell migration or the components of extracellular matrix. We provide clinical genetic testing strategies in the clinical evaluation that can identify a genetic cause in up to ∼30% of patients with non-isolated CDH and can be useful to refine prognosis, identify associated medical and neurodevelopmental issues to address, and inform family planning options.

Keywords: CDH; Chromosomal anomalies; Congenital diaphragmatic hernia; Gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Movement / genetics
  • Chromosome Aberrations
  • DNA Copy Number Variations
  • Exome Sequencing
  • Extracellular Matrix / genetics
  • Hernias, Diaphragmatic, Congenital / genetics*
  • Humans
  • Infant, Newborn
  • Mutation
  • Transcription Factors / genetics
  • Whole Genome Sequencing


  • Transcription Factors