Skip to main content
SpringerLink
Log in

Etiology of Congenital Colorectal Disease

  • Chapter
Constipation

  • 1318 Accesses

Conclusion

Hirschsprung first described HD in 1886, and since then many theories have been postulated to explain the genesis of this rather complex disease. Recent advances and studies in animal models have furnished a better understanding of the embryogenesis of the human enteric nervous system and the pathophysiology of HD. Genetic studies have identified various factors that can collectively influence the disease phenotype in HD. In humans ret, EDRNB, and EDN3 have been implicated in the etiology of HD. No one factor, however, can be singled out, as HD is a complex multigenic disorder. Future studies in identification of abnormal genes that cause dysganglionosis could help in the prevention and treatment of many of the disorders that have a genetic etiology. At this stage genetic counseling is still based on the length of the aganglionic segment. Future research will provide a better understanding of this complex genetic disorder and better means of counseling affected families. Understanding of the pathophysiology and its link to the disease phenotype of HD and its related diseases will also modify treatment options and help future generations of affected families.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Passarge E. The genetics of Hirschsprung’s disease. N Engl J Med 1967;276:138–143.

    Article  PubMed  CAS  Google Scholar 

  2. Kleinhaus S, Boley SJ, Sheran M, Sieber WK. Hirschsprung’s disease: a survey of the members of the surgical section of the American Academy of Pediatrics. J Pediatr Surg 1979;14:588–597.

    PubMed  CAS  Google Scholar 

  3. Meier-Ruge W. Classification of malformations of colorectal innervation. Vech Dtsch Ges Pathol 1971;506:55.

    Google Scholar 

  4. Puri P, Lake BD, Nixon HH, et al. Neuronal colonic dysplasia: an unusual association of Hirschsprung’s disease. J Pediatr Surg 1977;12:681–685.

    Article  PubMed  CAS  Google Scholar 

  5. Furness JB, Costa M. The enteric nervous system. 1987:65–69. New York Churchill Livingstone.

    Google Scholar 

  6. Gershon MD, Kirchgessner AL. Functional anatomy of the enteric nervous system. In Physiology of the gastrointestinal tract. 3rd Ed. Edited by Johnson LR, Alpers DH, Jocobson LR and Walsh JH. New York: Raven Press Vol. 1, 1994, 381–422.

    Google Scholar 

  7. Okamoto E, Ueda T. Embryogenesis of intramural ganglia of the gut and its relationship to Hirschsprung’s disease. J Pediatr Surg 1967;14:437–443.

    Article  Google Scholar 

  8. LeDourin NM. Experimental analysis of the migration and differentiation of neuroblasts of the autonomous nervous system and neuroectodermal mesenchymal derivatives using a biochemical marking techniques. Dev Biol 1973;41:162–184.

    Article  Google Scholar 

  9. LeDourin NM. The migration of neural crest cells to the wall of the digestive tract in avian embryo. J Embryol Exp Morphol 1973;30:31–48.

    Google Scholar 

  10. Erickson CA. Control of neural crest cell migration in avian embryo. Dev Biol 1985;111:138–157.

    Article  PubMed  CAS  Google Scholar 

  11. Weston JA. The migration and differentiation of neural crest cells. Adv Morphol 1970;8:41–114.

    CAS  Google Scholar 

  12. Newgreen DF. Control of the directional migration of migration of mesenchyme cells and neurites. Semin Dev Biol 1990;1:301–311.

    Google Scholar 

  13. Akitaya T, Bronner-Fraser M. Expression of cell adhesion molecules during initiation and cessation of neural crest migration. Dev Dynam 1992;194:12–20.

    CAS  Google Scholar 

  14. Pomeranz HD, Sherman DI, Smalheiser NR, et al. Expression of a neurally related laminin binding protein by neural crest-derived cells that colonize the gut: relationship to the formation of enteric ganglia. J Comp Neurol 1991;313:625–642.

    Article  PubMed  CAS  Google Scholar 

  15. Bilozur ME, Hay ED. Neural crest migration in 3D extracellular matrix utilizes laminin, fibronectin or collagen. Dev Biol 1988;125:19–33.

    Article  PubMed  CAS  Google Scholar 

  16. Engvall E, Davis GE, Dickerson K, et al. Mapping of domains in human laminin using monoclonal antibodies: localization of the neurite promoting site. J Cell Biol 1986;103:1321–1329.

    Article  Google Scholar 

  17. Bolande RP. Animal model of human disease. Hirschsprung’s disease, aganglionic or hypoganglionic megacolon: animal model. Aganglionic megacolon in piebald and spotted mutant mouse strains. Am J Pathol 1975;79:189–192.

    PubMed  CAS  Google Scholar 

  18. Lane PW. Association of megacolon with recessive spotting genes in the mouse. J Hered 1966;108:29–31.

    Google Scholar 

  19. Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung’s disease. Am J Hum Genet 1990;46:568–580.

    PubMed  CAS  Google Scholar 

  20. Pachynis V, Mankoo B, Constantini F. Expression of c-ret protooncogene during mouse embryogenesis. Development 1993;119:1005–1017.

    Google Scholar 

  21. Jing S, Wen D, Yu Y, et al. GDNF-induced activation of the Ret protein tyrosine kinase is mediated by GDNFRalpha a novel receptor for GDNBF. Cell 1996;85:1113–1124.

    Article  PubMed  CAS  Google Scholar 

  22. Martucciello G, Favre A, Takahashi M, Jasonni V. Immunohistochemical localization of Ret protein in Hirschsprung’s disease. J Pediatr Surg 1995;30:433–436.

    Article  PubMed  CAS  Google Scholar 

  23. Baynash AG, Hosoda K, Giaid A, et al. Interaction of endothelin 3 with endothelin b receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 1994;79:1277–1285.

    Article  PubMed  CAS  Google Scholar 

  24. Hosoda K, Hammer RE, Richardson JA, et al. Targeted and natural (piebald-lethal) mutation of endothelin-B receptor gene in mutagenic Hirschsprung’s disease. Cell 1994;79:1267–1276.

    Article  PubMed  CAS  Google Scholar 

  25. Charkravarty A. Endothelin receptor mediated signalling in Hirschsprung’s disease. Hum Mol Genet 1996;5:303–307.

    Google Scholar 

  26. Kusafuka T, Wang YP. Novel mutation of the endothelin-B receptor gene in isolated patients wih Hirschsprung’s disease. Hum Mol Genet 1996;5:347–349.

    Article  PubMed  CAS  Google Scholar 

  27. Stoss F, Meier-Ruge W. Experience with neuronal intestinal dysplasia (NID) in adults. Eur J Pediatr Surg 1994;4:298–302.

    Article  PubMed  CAS  Google Scholar 

  28. Schuffler MD, Pagon RB, Schwartz R, Bill AH. Visceral myopathy of the gastrointestinal tract. Gasteroenterology 1988;94:892–898.

    CAS  Google Scholar 

  29. Ionasescu V, Ionasescu R, Anuras S. Alterations in synthesis of contractile protein in fresh and cultured stomach smooth muscle in familial visceral myopathy. Gasteroenterology 1981;80:1182.

    Google Scholar 

  30. Lowsky R, Davidson G, Wolman S, et al. Familial visceral myopathy associated with mitochondrial myopathy. Gut 1993;34:279–283.

    PubMed  CAS  Google Scholar 

  31. Brown RA. Disorders and Congenital Malformations Associated with Hirschsprung’s Disease. Harwood Academic Publishers, Amsterdam, 2000.

    Google Scholar 

  32. Puffenberger EG, Hosada K, Washington SS. A missense mutation of the Endothelin-B receptor gene in multigenic Hirschsprung’s disease. Cell 1994;79:1257–1266.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA

    Massarat Zutshi MD & Tracy L. Hull MD

Authors
  1. Massarat Zutshi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tracy L. Hull MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Cleveland Clinic Florida, Weston, FL, USA

    Steven D. Wexner MD, FACS, FRCS, FRCS (Ed) (21st Century Oncology Chair in Colorectal Surgery Chairman, Department of Colorectal Surgery Chief of Staff, Professor of Surgery and Clinical Professor of Surgery) (21st Century Oncology Chair in Colorectal Surgery Chairman, Department of Colorectal Surgery Chief of Staff, Professor of Surgery and Clinical Professor of Surgery)

  2. Ohio State University Health Sciences Center at the Cleveland Clinic Foundation, Columbus, OH, USA

    Steven D. Wexner MD, FACS, FRCS, FRCS (Ed) (21st Century Oncology Chair in Colorectal Surgery Chairman, Department of Colorectal Surgery Chief of Staff, Professor of Surgery and Clinical Professor of Surgery) (21st Century Oncology Chair in Colorectal Surgery Chairman, Department of Colorectal Surgery Chief of Staff, Professor of Surgery and Clinical Professor of Surgery)

  3. University of South Florida College of Medicine, Tampa, FL, USA

    Steven D. Wexner MD, FACS, FRCS, FRCS (Ed) (21st Century Oncology Chair in Colorectal Surgery Chairman, Department of Colorectal Surgery Chief of Staff, Professor of Surgery and Clinical Professor of Surgery) (21st Century Oncology Chair in Colorectal Surgery Chairman, Department of Colorectal Surgery Chief of Staff, Professor of Surgery and Clinical Professor of Surgery)

  4. Charles E. Schmitt College of Science, Florida Atlantic University, Boca Raton, FL, USA

    Steven D. Wexner MD, FACS, FRCS, FRCS (Ed) (21st Century Oncology Chair in Colorectal Surgery Chairman, Department of Colorectal Surgery Chief of Staff, Professor of Surgery and Clinical Professor of Surgery) (21st Century Oncology Chair in Colorectal Surgery Chairman, Department of Colorectal Surgery Chief of Staff, Professor of Surgery and Clinical Professor of Surgery)

  5. University of Hull, Cattingham, UK

    Graeme S. Duthie MD, FRCS, FRCSEd (Reader in Surgery and Honorary Consultant Colorectal Surgeon) (Reader in Surgery and Honorary Consultant Colorectal Surgeon)

  6. Hull and East Yorkshire NHS Trust, Castle Hill Hospital, Cottingham, UK

    Graeme S. Duthie MD, FRCS, FRCSEd (Reader in Surgery and Honorary Consultant Colorectal Surgeon) (Reader in Surgery and Honorary Consultant Colorectal Surgeon)

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag London Limited

About this chapter

Cite this chapter

Zutshi, M., Hull, T.L. (2006). Etiology of Congenital Colorectal Disease. In: Wexner, S.D., Duthie, G.S. (eds) Constipation. Springer, London. https://doi.org/10.1007/978-1-84628-275-1_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-84628-275-1_2

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-85233-724-7

  • Online ISBN: 978-1-84628-275-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation