Retinoid pathway and congenital diaphragmatic hernia: hypothesis from the analysis of chromosomal abnormalities

Fetal Diagn Ther. 2010;28(3):129-39. doi: 10.1159/000313331. Epub 2010 May 26.


Background/objectives: Although there is strong evidence implicating genetic factors in congenital diaphragmatic hernia (CDH) pathogenesis, few causal genes have been identified. Many studies suggest that early disruption of the retinoid signaling pathway during gestation may contribute to CDH etiology. Chromosome abnormalities are detected in 10-20% of CDH cases. Chromosomal regions that are involved in balanced translocations or are recurrently deleted or duplicated in patients with CDH are of particular interest to researchers because they are more likely to harbor genes that cause or predispose one to the development of CDH. The aim of this review was to select chromosome loci which have been shown to be associated with CDH and to investigate if these loci contain candidate genes involved in the retinoic signaling pathway.

Data sources: We have re-examined the known CDH-critical chromosomal loci and searched in available databases, such as the UCSC Genome Browser and OMIM, to see whether candidate genes related to the retinoid pathway were present within these loci.

Results: Twelve retinoid-related genes have been proposed as potential candidates. Among them, COUP-TFII, FOG2 and GATA4 have already been well studied, especially in animal models. We propose other candidates such as STRA6, LRAT, CRBP1, CRBP2 and CRABP1 are directly implicated in retinoic acid metabolism.

Conclusion: The identification of CDH-related genes and pathways affecting a normal diaphragm will contribute to the understanding of the pathophysiology of this severe embryopathy and might help to facilitate prenatal management and devise more individual treatment strategies. Further studies are necessary to screen large cohorts of patients with CDH for microimbalances or de novo mutations in these candidate genes. Moreover, functional analyses are needed to establish their exact role in CDH etiology.

Publication types

  • Review

MeSH terms

  • COUP Transcription Factor II / genetics
  • Chromosome Aberrations*
  • Genetic Loci
  • Hernia, Diaphragmatic / metabolism
  • Hernias, Diaphragmatic, Congenital*
  • Humans
  • Retinoids / genetics*
  • Retinoids / metabolism*
  • Retinol-Binding Proteins / genetics
  • Retinol-Binding Proteins / metabolism


  • COUP Transcription Factor II
  • Retinoids
  • Retinol-Binding Proteins