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Chronic Megacolon Presenting in Adolescents or Adults: Clinical Manifestations, Diagnosis, and Genetic Associations

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Abstract

Objective

Chronic megacolon is rarely encountered in clinical practice beyond infancy or early childhood. Most cases are sporadic, and some are familial megacolon and present during adolescence or adulthood. There is a need for diagnostic criteria and identifying genetic variants reported in non-Hirschsprung’s megacolon.

Methods

PubMed search was conducted using specific key words.

Results

This article reviews the clinical manifestations, current diagnostic criteria, and intraluminal measurements of colonic compliance to confirm the diagnosis when the radiological imaging is not conclusive. Normal ranges of colonic compliance at 20, 30, and 44 mmHg distension are provided. The diverse genetic associations with chronic acquired megacolon beyond childhood are reviewed, including the potential association of SEMA3F gene in a family with megacolon.

Conclusions

Measuring colonic compliance could be standardized and simplified by measuring volume at 20, 30, and 44 mmHg distension to identify megacolon when radiology is inconclusive. Diverse genetic associations with chronic acquired megacolon beyond childhood have been identified.

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References

  1. Halder SL, Locke GR 3rd, Schleck CD, Zinsmeister AR, Melton LJ 3rd, Talley NJ. Natural history of functional gastrointestinal disorders: a 12-year longitudinal population-based study. Gastroenterology. 2007;133:799–807.

    Article  PubMed  Google Scholar 

  2. Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF, Taminiau J. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology. 2006;130:1519–1526.

    Article  PubMed  Google Scholar 

  3. Cuda T, Gunnarsson R, de Costa A. Symptoms and diagnostic criteria of acquired Megacolon—a systematic literature review. BMC Gastroenterol. 2018;18:25.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Goulston E. Diverticular disease of the colon and megacolon. Incidence in a psychiatric centre compared with a teaching hospital. Med J Aust. 1976;2:863–864.

    Article  CAS  PubMed  Google Scholar 

  5. O’Dwyer RH, Acosta A, Camilleri M, Burton D, Busciglio I, Bharucha AE. Clinical features and colonic motor disturbances in chronic megacolon in adults. Dig Dis Sci. 2015;60:2398–2407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Vijayvargiya P, Camilleri M. Proximal megacolon in an adult. Clin Gastroenterol Hepatol. 2014;12:e83–e84.

    Article  PubMed  Google Scholar 

  7. Lee JI, Park H, Kamm MA, Talbot IC. Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon. J Gastroenterol Hepatol. 2005;20:1292–1298.

    Article  PubMed  Google Scholar 

  8. Faussone-Pellegrini MS, Fociani P, Buffa R, Basilisco G. Loss of interstitial cells and a fibromuscular layer on the luminal side of the colonic circular muscle presenting as megacolon in an adult patient. Gut. 1999;45:775–779.

    Article  CAS  PubMed  Google Scholar 

  9. Ohkubo H, Masaki T, Matsuhashi N, et al. Histopathologic findings in patients with idiopathic megacolon: a comparison between dilated and non-dilated loops. Neurogastroenterol Motil. 2014;26:571–580.

    Article  CAS  PubMed  Google Scholar 

  10. Wedel T, Van Eys GJ, Waltregny D, Glénisson W, Castronovo V, Vanderwinden JM. Novel smooth muscle markers reveal abnormalities of the intestinal musculature in severe colorectal motility disorders. Neurogastroenterol Motil. 2006;18:526–538.

    Article  CAS  PubMed  Google Scholar 

  11. Gattuso JM, Kamm MA, Talbot JC. Pathology of idiopathic megarectum and megacolon. Gut. 1997;41:252–257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lake JI, Heuckeroth RO. Enteric nervous system development: migration, differentiation, and disease. Am J Physiol Gastrointest Liver Physiol. 2013;305:G1–G24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008;45:1–14.

    Article  CAS  PubMed  Google Scholar 

  14. Krishnamurthy S, Schuffler MD. Pathology of neuromuscular disorders of the small intestine and colon. Gastroenterology. 1987;93:610–639.

    Article  CAS  PubMed  Google Scholar 

  15. Di Lorenzo C, Youssef NN. Diagnosis and management of intestinal motility disorders. Semin Pediatr Surg. 2010;19:50–58.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Iwashita T, Kruger GM, Pardal R, Kiel MJ, Morrison SJ. Hirschsprung disease is linked to defects in neural crest stem cell function. Science. 2003;301:972–976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Porokuokka LL, Virtanen HT, Lindén J, et al. GFRA1 underexpression causes Hirschsprung’s disease and associated enterocolitis in mice. Cell Mol Gastroenterol Hepatol. 2018. https://doi.org/10.1016/j.jcmgh.2018.12.007.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Leon TY, Ngan ES, Poon HC, et al. Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3. J Pediatr Surg. 2009;44:1904–1912.

    Article  PubMed  Google Scholar 

  20. Garcia-Barcelo MM, Lau DK, Ngan ES, et al. Evaluation of the NK2 homeobox 1 gene (NKX2-1) as a Hirschsprung’s disease locus. Ann Hum Genet. 2008;72:170–177.

    Article  CAS  PubMed  Google Scholar 

  21. Zhou R, Niwa S, Homma N, Takei Y, Hirokawa N. KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development. Cell. 2009;139:802–813.

    Article  CAS  PubMed  Google Scholar 

  22. Clarke NF, Kolski H, Dye DE, et al. Mutations in TPM3 are a common cause of congenital fiber type disproportion. Ann Neurol. 2008;63:329–337.

    Article  CAS  PubMed  Google Scholar 

  23. Lehtokari VL, Pelin K, Donner K, et al. Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin. Eur J Hum Genet. 2008;16:1055–1061.

    Article  CAS  PubMed  Google Scholar 

  24. Gattuso JM, Smith VV, Kamm MA. Altered contractile proteins and neural innervation in idiopathic megarectum and megacolon. Histopathology. 1998;33:34–38.

    Article  CAS  PubMed  Google Scholar 

  25. Camilleri M, Wieben E, Eckert D, et al. Familial chronic megacolon presenting in childhood or adulthood: Seeking the presumed gene association. Neurogastroenterol Motil. 2019;20:e13550. https://doi.org/10.1111/nmo.13550.

    Article  CAS  Google Scholar 

  26. Mungan Z, Akyüz F, Bugra Z, et al. Familial visceral myopathy with pseudo-obstruction, megaduodenum, Barrett’s esophagus, and cardiac abnormalities. Am J Gastroenterol. 2003;98:2556–2560.

    Article  PubMed  Google Scholar 

  27. Gunadi, Makhmudi A, Agustriani N, Rochadi. Effects of SEMA3 polymorphisms in Hirschsprung disease patients. Pediatr Surg Int. 2016;32:1025–1028.

    Article  CAS  PubMed  Google Scholar 

  28. Kapoor A, Jiang Q, Chatterjee S, et al. Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms. Hum Mol Genet. 2015;24:2997–3003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jiang Q, Arnold S, Heanue T, et al. Functional loss of semaphorin 3C and/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability. Am J Hum Genet. 2015;96:581–596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gershon MD. Developmental determinants of the independence and complexity of the enteric nervous system. Trends Neurosci. 2010;33:446–456.

    Article  CAS  PubMed  Google Scholar 

  31. Gershon MD, Payette RF, Rothman TP. Development of the enteric nervous system. Fed Proc. 1983;42:1620–1625.

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank Mrs. Cindy Stanislav for excellent secretarial assistance.

Funding

Dr. Camilleri is funded by grants RO1-DK115950 and R01-DK67071 from National Institutes of Health.

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Authors and Affiliations

  1. Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton Bldg., Rm. 8-110, 200 First Street S.W., Rochester, MN, 55905, USA

    Xiao Jing Wang & Michael Camilleri

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  1. Xiao Jing Wang
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  2. Michael Camilleri
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Correspondence to Michael Camilleri.

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Wang, X.J., Camilleri, M. Chronic Megacolon Presenting in Adolescents or Adults: Clinical Manifestations, Diagnosis, and Genetic Associations. Dig Dis Sci 64, 2750–2756 (2019). https://doi.org/10.1007/s10620-019-05605-7

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  • DOI: https://doi.org/10.1007/s10620-019-05605-7

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