Congenital diaphragmatic hernias: from genes to mechanisms to therapies
Congenital diaphragmatic hernias (CDHs) and structural anomalies of the diaphragm are a common class of congenital birth defects that are associated with significant morbidity and mortality due to associated pulmonary hypoplasia, pulmonary hypertension and heart failure. In ∼30% of CDH patients, gen...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2017-08-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/10/8/955 |
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| author | Gabrielle Kardon Kate G. Ackerman David J. McCulley Yufeng Shen Julia Wynn Linshan Shang Eric Bogenschutz Xin Sun Wendy K. Chung |
| author_facet | Gabrielle Kardon Kate G. Ackerman David J. McCulley Yufeng Shen Julia Wynn Linshan Shang Eric Bogenschutz Xin Sun Wendy K. Chung |
| author_sort | Gabrielle Kardon |
| collection | DOAJ |
| description | Congenital diaphragmatic hernias (CDHs) and structural anomalies of the diaphragm are a common class of congenital birth defects that are associated with significant morbidity and mortality due to associated pulmonary hypoplasia, pulmonary hypertension and heart failure. In ∼30% of CDH patients, genomic analyses have identified a range of genetic defects, including chromosomal anomalies, copy number variants and sequence variants. The affected genes identified in CDH patients include transcription factors, such as GATA4, ZFPM2, NR2F2 and WT1, and signaling pathway components, including members of the retinoic acid pathway. Mutations in these genes affect diaphragm development and can have pleiotropic effects on pulmonary and cardiac development. New therapies, including fetal endoscopic tracheal occlusion and prenatal transplacental fetal treatments, aim to normalize lung development and pulmonary vascular tone to prevent and treat lung hypoplasia and pulmonary hypertension, respectively. Studies of the association between particular genetic mutations and clinical outcomes should allow us to better understand the origin of this birth defect and to improve our ability to predict and identify patients most likely to benefit from specialized treatment strategies. |
| first_indexed | 2024-12-11T06:46:20Z |
| format | Article |
| id | doaj.art-901141c9574e40c49a93391a1c8d726a |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-11T06:46:20Z |
| publishDate | 2017-08-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-901141c9574e40c49a93391a1c8d726a2022-12-22T01:17:03ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112017-08-0110895597010.1242/dmm.028365028365Congenital diaphragmatic hernias: from genes to mechanisms to therapiesGabrielle Kardon0Kate G. Ackerman1David J. McCulley2Yufeng Shen3Julia Wynn4Linshan Shang5Eric Bogenschutz6Xin Sun7Wendy K. Chung8 Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Departments of Pediatrics (Critical Care) and Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA Department of Pediatrics, University of Wisconsin, Madison, WI 53792, USA Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA Departments of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA Departments of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA Congenital diaphragmatic hernias (CDHs) and structural anomalies of the diaphragm are a common class of congenital birth defects that are associated with significant morbidity and mortality due to associated pulmonary hypoplasia, pulmonary hypertension and heart failure. In ∼30% of CDH patients, genomic analyses have identified a range of genetic defects, including chromosomal anomalies, copy number variants and sequence variants. The affected genes identified in CDH patients include transcription factors, such as GATA4, ZFPM2, NR2F2 and WT1, and signaling pathway components, including members of the retinoic acid pathway. Mutations in these genes affect diaphragm development and can have pleiotropic effects on pulmonary and cardiac development. New therapies, including fetal endoscopic tracheal occlusion and prenatal transplacental fetal treatments, aim to normalize lung development and pulmonary vascular tone to prevent and treat lung hypoplasia and pulmonary hypertension, respectively. Studies of the association between particular genetic mutations and clinical outcomes should allow us to better understand the origin of this birth defect and to improve our ability to predict and identify patients most likely to benefit from specialized treatment strategies.http://dmm.biologists.org/content/10/8/955Structural birth defectsCongenital diaphragmatic hernia (CDH)DiaphragmPulmonary hypoplasiaPulmonary hypertensionCongenital heart disease (CHD)Genetics |
| spellingShingle | Gabrielle Kardon Kate G. Ackerman David J. McCulley Yufeng Shen Julia Wynn Linshan Shang Eric Bogenschutz Xin Sun Wendy K. Chung Congenital diaphragmatic hernias: from genes to mechanisms to therapies Disease Models & Mechanisms Structural birth defects Congenital diaphragmatic hernia (CDH) Diaphragm Pulmonary hypoplasia Pulmonary hypertension Congenital heart disease (CHD) Genetics |
| title | Congenital diaphragmatic hernias: from genes to mechanisms to therapies |
| title_full | Congenital diaphragmatic hernias: from genes to mechanisms to therapies |
| title_fullStr | Congenital diaphragmatic hernias: from genes to mechanisms to therapies |
| title_full_unstemmed | Congenital diaphragmatic hernias: from genes to mechanisms to therapies |
| title_short | Congenital diaphragmatic hernias: from genes to mechanisms to therapies |
| title_sort | congenital diaphragmatic hernias from genes to mechanisms to therapies |
| topic | Structural birth defects Congenital diaphragmatic hernia (CDH) Diaphragm Pulmonary hypoplasia Pulmonary hypertension Congenital heart disease (CHD) Genetics |
| url | http://dmm.biologists.org/content/10/8/955 |
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