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. 1996 Jan;74(1):5–7. doi: 10.1136/adc.74.1.5

Hirschprung's disease.

P B Sullivan 1
PMCID: PMC1511606  PMID: 8660047

Abstract

Current evidence on the pathogenesis of Hirschprung's disease, then, favours the 'abnormal microenvironment' hypothesis wherein the developing and migrating normal neural crest cells confront a segmentally abnormal and hostile microenvironment in the colon. This hypothesis would account both for the congenital absence of ganglion cells in the wall of colon and also for the range of enteric neuronal abnormalities encountered including neuronal dysplasia, hypoganglionosis, and zonal aganglionosis. The abnormal constitution of the mesenchymal and basement membrane extracellular matrix in the affected segment of colon is presumably genetically determined and further understanding of the pathogenesis of this disorder will emerge as molecular geneticists characterise the specific genes and gene products associated with Hirschprung's disease. Advances in this field should permit gene probes to be developed to facilitate prenatal and postnatal diagnosis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angrist M., Kauffman E., Slaugenhaupt S. A., Matise T. C., Puffenberger E. G., Washington S. S., Lipson A., Cass D. T., Reyna T., Weeks D. E. A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10. Nat Genet. 1993 Aug;4(4):351–356. doi: 10.1038/ng0893-351. [DOI] [PubMed] [Google Scholar]
  2. Bealer J. F., Natuzzi E. S., Flake A. W., Adzick N. S., Harrison M. R. Effect of nitric oxide on the colonic smooth muscle of patients with Hirschsprung's disease. J Pediatr Surg. 1994 Aug;29(8):1025–1029. doi: 10.1016/0022-3468(94)90272-0. [DOI] [PubMed] [Google Scholar]
  3. Edery P., Lyonnet S., Mulligan L. M., Pelet A., Dow E., Abel L., Holder S., Nihoul-Fékété C., Ponder B. A., Munnich A. Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):378–380. doi: 10.1038/367378a0. [DOI] [PubMed] [Google Scholar]
  4. Edery P., Pelet A., Mulligan L. M., Abel L., Attié T., Dow E., Bonneau D., David A., Flintoff W., Jan D. Long segment and short segment familial Hirschsprung's disease: variable clinical expression at the RET locus. J Med Genet. 1994 Aug;31(8):602–606. doi: 10.1136/jmg.31.8.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Engum S. A., Petrites M., Rescorla F. J., Grosfeld J. L., Morrison A. M., Engles D. Familial Hirschsprung's disease: 20 cases in 12 kindreds. J Pediatr Surg. 1993 Oct;28(10):1286–1290. doi: 10.1016/s0022-3468(05)80314-8. [DOI] [PubMed] [Google Scholar]
  6. Fujimoto T., Hata J., Yokoyama S., Mitomi T. A study of the extracellular matrix protein as the migration pathway of neural crest cells in the gut: analysis in human embryos with special reference to the pathogenesis of Hirschsprung's disease. J Pediatr Surg. 1989 Jun;24(6):550–556. doi: 10.1016/s0022-3468(89)80504-4. [DOI] [PubMed] [Google Scholar]
  7. Gelfond M., Rozen P., Gilat T. Isosorbide dinitrate and nifedipine treatment of achalasia: a clinical, manometric and radionuclide evaluation. Gastroenterology. 1982 Nov;83(5):963–969. [PubMed] [Google Scholar]
  8. Gershon M. D., Chalazonitis A., Rothman T. P. From neural crest to bowel: development of the enteric nervous system. J Neurobiol. 1993 Feb;24(2):199–214. doi: 10.1002/neu.480240207. [DOI] [PubMed] [Google Scholar]
  9. Huizinga J. D., Tomlinson J., Pintin-Quezada J. Involvement of nitric oxide in nerve-mediated inhibition and action of vasoactive intestinal peptide in colonic smooth muscle. J Pharmacol Exp Ther. 1992 Feb;260(2):803–808. [PubMed] [Google Scholar]
  10. Jacobs-Cohen R. J., Payette R. F., Gershon M. D., Rothman T. P. Inability of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice: requirement for a permissive microenvironment. J Comp Neurol. 1987 Jan 15;255(3):425–438. doi: 10.1002/cne.902550309. [DOI] [PubMed] [Google Scholar]
  11. Kapur R. P. Contemporary approaches toward understanding the pathogenesis of Hirschsprung disease. Pediatr Pathol. 1993 Jan-Feb;13(1):83–100. doi: 10.3109/15513819309048196. [DOI] [PubMed] [Google Scholar]
  12. Kapur R. P., Yost C., Palmiter R. D. Aggregation chimeras demonstrate that the primary defect responsible for aganglionic megacolon in lethal spotted mice is not neuroblast autonomous. Development. 1993 Mar;117(3):993–999. doi: 10.1242/dev.117.3.993. [DOI] [PubMed] [Google Scholar]
  13. Larsson L. T., Malmfors G., Wahlestedt C., Leander S., Håkanson R. Hirschsprung's disease: a comparison of the nervous control of ganglionic and aganglionic smooth muscle in vitro. J Pediatr Surg. 1987 May;22(5):431–435. doi: 10.1016/s0022-3468(87)80263-4. [DOI] [PubMed] [Google Scholar]
  14. Larsson L. T., Shen Z., Ekblad E., Sundler F., Alm P., Andersson K. E. Lack of neuronal nitric oxide synthase in nerve fibers of aganglionic intestine: a clue to Hirschsprung's disease. J Pediatr Gastroenterol Nutr. 1995 Jan;20(1):49–53. doi: 10.1097/00005176-199501000-00009. [DOI] [PubMed] [Google Scholar]
  15. Larsson L. T., Sundler F. Is the reduction of VIP the clue to the pathophysiology of Hirschsprung's disease? Z Kinderchir. 1990 Jun;45(3):164–166. doi: 10.1055/s-2008-1042574. [DOI] [PubMed] [Google Scholar]
  16. Lyonnet S., Bolino A., Pelet A., Abel L., Nihoul-Fékété C., Briard M. L., Mok-Siu V., Kaariainen H., Martucciello G., Lerone M. A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10. Nat Genet. 1993 Aug;4(4):346–350. doi: 10.1038/ng0893-346. [DOI] [PubMed] [Google Scholar]
  17. O'Kelly T. J., Davies J. R., Tam P. K., Brading A. F., Mortensen N. J. Abnormalities of nitric-oxide-producing neurons in Hirschsprung's disease: morphology and implications. J Pediatr Surg. 1994 Feb;29(2):294–300. doi: 10.1016/0022-3468(94)90335-2. [DOI] [PubMed] [Google Scholar]
  18. Parikh D. H., Tam P. K., Lloyd D. A., Van Velzen D., Edgar D. H. Quantitative and qualitative analysis of the extracellular matrix protein, laminin, in Hirschsprung's disease. J Pediatr Surg. 1992 Aug;27(8):991–996. doi: 10.1016/0022-3468(92)90545-i. [DOI] [PubMed] [Google Scholar]
  19. Payette R. F., Tennyson V. M., Pomeranz H. D., Pham T. D., Rothman T. P., Gershon M. D. Accumulation of components of basal laminae: association with the failure of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice. Dev Biol. 1988 Feb;125(2):341–360. doi: 10.1016/0012-1606(88)90217-5. [DOI] [PubMed] [Google Scholar]
  20. Puffenberger E. G., Hosoda K., Washington S. S., Nakao K., deWit D., Yanagisawa M., Chakravart A. A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. Cell. 1994 Dec 30;79(7):1257–1266. doi: 10.1016/0092-8674(94)90016-7. [DOI] [PubMed] [Google Scholar]
  21. Romanska H. M., Bishop A. E., Brereton R. J., Spitz L., Polak J. M. Immunocytochemistry for neuronal markers shows deficiencies in conventional histology in the treatment of Hirschsprung's disease. J Pediatr Surg. 1993 Aug;28(8):1059–1062. doi: 10.1016/0022-3468(93)90519-q. [DOI] [PubMed] [Google Scholar]
  22. Romeo G., Ronchetto P., Luo Y., Barone V., Seri M., Ceccherini I., Pasini B., Bocciardi R., Lerone M., Käriäinen H. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):377–378. doi: 10.1038/367377a0. [DOI] [PubMed] [Google Scholar]
  23. Russell M. B., Russell C. A., Fenger K., Niebuhr E. Familial occurrence of Hirschsprung's disease. Clin Genet. 1994 May;45(5):231–235. doi: 10.1111/j.1399-0004.1994.tb04147.x. [DOI] [PubMed] [Google Scholar]
  24. Shen Z., Larsson L. T., Malmfors G., Absood A., Håkanson R., Sundler F. A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: evidence for reduced content in Hirschsprung's disease. Cell Tissue Res. 1992 Aug;269(2):369–374. doi: 10.1007/BF00319630. [DOI] [PubMed] [Google Scholar]
  25. Stannard V. A., Fowler C., Robinson L., Besner G., Glick P. L., Allen J. E., Jewett T. C., Cooney D. R. Familial Hirschsprung's disease: report of autosomal dominant and probable recessive X-linked kindreds. J Pediatr Surg. 1991 May;26(5):591–594. doi: 10.1016/0022-3468(91)90714-5. [DOI] [PubMed] [Google Scholar]
  26. Tam P. K., Boyd G. P. New insights into peptidergic abnormalities in Hirschsprung's disease by wholemount immunohistochemistry. J Pediatr Surg. 1991 May;26(5):595–597. doi: 10.1016/0022-3468(91)90715-6. [DOI] [PubMed] [Google Scholar]
  27. Tam P. K., Lister J. Development profile of neuron-specific enolase in human gut and its implications in Hirschsprung's disease. Gastroenterology. 1986 Jun;90(6):1901–1906. doi: 10.1016/0016-5085(86)90259-3. [DOI] [PubMed] [Google Scholar]
  28. Tsuto T., Obata-Tsuto H. L., Iwai N., Takahashi T., Ibata Y. Fine structure of neurons synthesizing vasoactive intestinal peptide in the human colon from patients with Hirschsprung's disease. Histochemistry. 1989;93(1):1–8. doi: 10.1007/BF00266839. [DOI] [PubMed] [Google Scholar]
  29. Tsuto T., Okamura H., Fukui K., Obata-Tsuto H. L., Terubayashi H., Yanagihara J., Iwai N., Majima S., Yanaihara N., Ibata Y. Immunohistochemical investigations of gut hormones in the colon of patients with Hirschsprung's disease. J Pediatr Surg. 1985 Jun;20(3):266–270. doi: 10.1016/s0022-3468(85)80118-4. [DOI] [PubMed] [Google Scholar]
  30. Vanderwinden J. M., De Laet M. H., Schiffmann S. N., Mailleux P., Lowenstein C. J., Snyder S. H., Vanderhaeghen J. J. Nitric oxide synthase distribution in the enteric nervous system of Hirschsprung's disease. Gastroenterology. 1993 Oct;105(4):969–973. doi: 10.1016/0016-5085(93)90938-9. [DOI] [PubMed] [Google Scholar]

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