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Variants of Hirschsprung Disease

Pediatric Surgery

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Abstract

Variants of Hirschsprung disease (HD) are conditions that clinically resemble HD despite the presence of ganglion cells in rectal suction biopsies. The characterization and differentiation of various entities is mainly based on histological and immunohistochemical findings of biopsies from patients with functional intestinal obstruction.

Over the last decades, several groups focused on the investigation and definition of variant HD such as intestinal neuronal dysplasia, isolated hyperganglionosis, internal anal sphincter achalasia, immature ganglia, and smooth muscle cell disorders such as megacystis microcolon intestinal hypoperistalsis syndrome. However, definition of the above-mentioned entities remains a controversial issue and research is ongoing to standardize diagnostic criteria, specific therapy, and outcome criteria.

This chapter summarizes the current knowledge of the above-mentioned entities of variant HD.

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References

  • Berdon WE, Baker DH, Blanc WA, et al. Megacystis-microcolon-intestinal hypoperistalsis syndrome: a new cause of intestinal obstruction in the newborn. Report of radiologic findings in five newborn girls. AJR Am J Roentgenol. 1976;126:957–64.

    Article  CAS  PubMed  Google Scholar 

  • Bruder E, Meier-Ruge WA. Intestinal neuronal dysplasia type B: how do we understand it today? Pathologe. 2007;28:137–42. doi:10.1007/s00292-007-0894-x.

    Article  CAS  PubMed  Google Scholar 

  • Coerdt W, Michel JS, Rippin G, et al. Quantitative morphometric analysis of the submucous plexus in age-related control groups. Virchows Arch. 2004;444:239–46. doi:10.1007/s00428-003-0951-7.

    Article  PubMed  Google Scholar 

  • Costa M, Fava M, Seri M, et al. Evaluation of the HOX11L1 gene as a candidate for congenital disorders of intestinal innervation. J Med Genet. 2000;37:E9–9. doi:10.1136/jmg.37.7.e9.

  • De Caluwe D, Yoneda A, Akl U, Puri P. Internal anal sphincter achalasia: outcome after internal sphincter myectomy. J Pediatr Surg. 2001;36:736–8.

    Article  PubMed  Google Scholar 

  • Dingemann J, Puri P. Isolated hypoganglionosis: systematic review of a rare intestinal innervation defect. Pediatr Surg Int. 2010;26:1111–5. doi:10.1007/s00383-010-2693-3.

    Article  PubMed  Google Scholar 

  • Do MY, Myung SJ, Park HJ, et al. Novel classification and pathogenetic analysis of hypoganglionosis and adult-onset Hirschsprung’s disease. Dig Dis Sci. 2011;56:1818–27. doi:10.1007/s10620-010-1522-9.

    Article  PubMed  Google Scholar 

  • Doodnath R, Puri P. Internal anal sphincter achalasia. Semin Pediatr Surg. 2009a;18:246–8. doi:10.1053/j.sempedsurg.2009.07.006.

    Article  PubMed  Google Scholar 

  • Doodnath R, Puri P. Long-term outcome of internal sphincter myectomy in patients with internal anal sphincter achalasia. Pediatr Surg Int. 2009b;25:869–71. doi:10.1007/s00383-009-2436-5.

    Article  PubMed  Google Scholar 

  • Fadda B, Maier WA, Meier-Ruge W, et al. Neuronal intestinal dysplasia. Critical 10-years’ analysis of clinical and biopsy diagnosis. Z Kinderchir. 1983;38:305–11. doi:10.1055/s-2008-1059994.

    CAS  PubMed  Google Scholar 

  • Fava M, Borghini S, Cinti R, et al. HOX11L1: a promoter study to evaluate possible expression defects in intestinal motility disorders. Int J Mol Med. 2002;10:101–6.

    CAS  PubMed  Google Scholar 

  • Friedmacher F, Puri P. Comparison of posterior internal anal sphincter myectomy and intrasphincteric botulinum toxin injection for treatment of internal anal sphincter achalasia: a meta-analysis. Pediatr Surg Int. 2012;28:765–71. doi:10.1007/s00383-012-3123-5.

    Article  PubMed  Google Scholar 

  • Garel C, Dreux S, Philippe-Chomette P, et al. Contribution of fetal magnetic resonance imaging and amniotic fluid digestive enzyme assays to the evaluation of gastrointestinal tract abnormalities. Ultrasound Obstet Gynecol. 2006;28:282–91. doi:10.1002/uog.2799.

    Article  CAS  PubMed  Google Scholar 

  • Gath R, Goessling A, Keller KM, et al. Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease. Gut. 2001;48:671–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gillick J, Tazawa H, Puri P. Intestinal neuronal dysplasia: results of treatment in 33 patients. J Pediatr Surg. 2001;36:777–9. doi:10.1053/jpsu.2001.22959.

    Article  CAS  PubMed  Google Scholar 

  • Gosemann J-H, Puri P. Megacystis microcolon intestinal hypoperistalsis syndrome: systematic review of outcome. Pediatr Surg Int. 2011;27:1041–6. doi:10.1007/s00383-011-2954-9.

    Article  PubMed  Google Scholar 

  • Granero Cendon R, Millan Lopez A, Moya Jimenez MJ, et al. Intestinal neuronal dysplasia: association with digestive malformations. Cir Pediatr. 2007;20:166–8.

    CAS  PubMed  Google Scholar 

  • Hatano M, Aoki T, Dezawa M, et al. A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice. J Clin Invest. 1997;100:795–801. doi:10.1172/JCI119593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirakawa H, Kobayashi H, O’Briain DS, Puri P. Absence of NADPH-diaphorase activity in internal anal sphincter (IAS) achalasia. J Pediatr Gastroenterol Nutr. 1995;20:54–8.

    Article  CAS  PubMed  Google Scholar 

  • Holland-Cunz S, Krammer HJ, Suss A, et al. Molecular genetics of colorectal motility disorders. Eur J Pediatr Surg. 2003;13:146–51. doi:10.1055/s-2003-41767.

    Article  CAS  PubMed  Google Scholar 

  • Holschneider AM, Puri P, Homrighausen LH, Meier-Ruge W. Intestinal neuronal malformations (IND): clinical experience and treatment. In: Holschneider AM, Puri P, editors. Hirschsprung’s disease and allied disorders. Heidelberg: Springer; 2008. p. 229–51.

    Chapter  Google Scholar 

  • Inoue K, Shimotake T, Tomiyama H, Iwai N. Mutational analysis of the RET and GDNF gene in children with hypoganglionosis. Eur J Pediatr Surg. 2001;11:120–3. doi:10.1055/s-2001-13792.

    Article  CAS  PubMed  Google Scholar 

  • Knowles CH, De Giorgio R, Kapur RP, et al. The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group. 2010. p 882–7.

    Google Scholar 

  • Kobayashi H, Hirakawa H, Surana R, et al. Intestinal neuronal dysplasia is a possible cause of persistent bowel symptoms after pull-through operation for Hirschsprungs-disease. J Pediatr Surg. 1995;30:253–9.

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi H, Mahomed A, Puri P. Intestinal neuronal dysplasia in twins. J Pediatr Gastroenterol Nutr. 1996;22:398–401.

    Article  CAS  PubMed  Google Scholar 

  • Kohler M, Pease PW, Upadhyay V. Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in siblings: case report and review of the literature. Eur J Pediatr Surg. 2004;14:362–7. doi:10.1055/s-2004-821208.

    Article  CAS  PubMed  Google Scholar 

  • Koletzko S, Jesch I, Faus-Kebetaler T, et al. Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome. Gut. 1999;44:853–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lake BD. Intestinal neuronal dysplasia. Why does it only occur in parts of Europe? Virchows Arch. 1995;426:537–9.

    Article  CAS  PubMed  Google Scholar 

  • Lake BD, Puri P, Nixon HH, Claireaux AE. Hirschsprung’s disease: an appraisal of histochemically demonstrated acetylcholinesterase activity in suction rectal biopsy specimens as an aid to diagnosis. Arch Pathol Lab Med. 1978;102:244–7.

    CAS  PubMed  Google Scholar 

  • Loinaz C, Rodríguez MM, Kato T, et al. Intestinal and multivisceral transplantation in children with severe gastrointestinal dysmotility. J Pediatr Surg. 2005;40:1598–604. doi:10.1016/j.jpedsurg.2005.06.002.

    Article  PubMed  Google Scholar 

  • Martucciello G, Torre M, Pini Prato A, et al. Associated anomalies in intestinal neuronal dysplasia. J Pediatr Surg. 2002;37:219–23.

    Article  CAS  PubMed  Google Scholar 

  • Martucciello G, Pini Prato A, Puri P, et al. Controversies concerning diagnostic guidelines for anomalies of the enteric nervous system: a report from the fourth international symposium on Hirschsprung’s disease and related neurocristopathies. In: 2005 edn. 2005. p 1527–31.

    Google Scholar 

  • McNamara HM, Onwude JL, Thornton JG. Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report supporting autosomal recessive inheritance. Prenat Diagn. 1994;14:153–4.

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin D, Puri P. Familial megacystis microcolon intestinal hypoperistalsis syndrome: a systematic review. Pediatr Surg Int 2013;29:947–951.

    Google Scholar 

  • Meier-Ruge WA. Casuistic colon disorder with symptoms of Hirschsprung’s disease. Verh Dtsch Ges Pathol. 1971;55:506–10.

    CAS  PubMed  Google Scholar 

  • Meier-Ruge W. Ultrashort segment Hirschsprung disease. An objective picture of the disease substantiated by biopsy. Z Kinderchir. 1985;40:146–50. doi:10.1055/s-2008-1059734.

    CAS  PubMed  Google Scholar 

  • Meier-Ruge W. Epidemiology of congenital innervation defects of the distal colon. Virchows Arch A Pathol Anat Histopathol. 1992;420:171–7.

    Article  CAS  PubMed  Google Scholar 

  • Meier-Ruge WA, Bruder E. Pathology of chronic constipation in pediatric and adult coloproctology. Pathobiology. 2005;72:1–102.

    Article  PubMed  Google Scholar 

  • Meier-Ruge WA, Brunner LA, Engert J, et al. A correlative morphometric and clinical investigation of hypoganglionosis of the colon in children. Eur J Pediatr Surg. 1999;9:67–74. doi:10.1055/s-2008-1072216.

    Article  CAS  PubMed  Google Scholar 

  • Meier-Ruge WA, Ammann K, Bruder E, et al. Updated results on intestinal neuronal dysplasia (IND B). Eur J Pediatr Surg. 2004;14:384–91. doi:10.1055/s-2004-821120.

    Article  CAS  PubMed  Google Scholar 

  • Milla PJ, Smith VV. Intestinal neuronal dysplasia. J Pediatr Gastroenterol Nutr. 1993;17:356–7.

    Article  CAS  PubMed  Google Scholar 

  • Montedonico S, Acevedo S, Fadda B. Clinical aspects of intestinal neuronal dysplasia. J Pediatr Surg. 2002;37:1772–4. doi:10.1053/jpsu.2002.36720.

    Article  PubMed  Google Scholar 

  • Montedonico S, Caceres P, Munoz N, et al. Histochemical staining for intestinal dysganglionosis: over 30 years experience with more than 1,500 biopsies. Pediatr Surg Int. 2011;27:479–86. doi:10.1007/s00383-010-2849-1.

    Article  PubMed  Google Scholar 

  • Moore SW. Advances in understanding functional variations in the Hirschsprung disease spectrum (variant Hirschsprung disease). Pediatr Surg Int. 2016; doi:10.1007/s00383-016-4038-3.

    PubMed  Google Scholar 

  • Moore SW, Kaschula ROC, Cywes S. Familial and genetic-aspects of neuronal intestinal dysplasia and Hirschsprungs-disease. Pediatr Surg Int. 1993;8:406–9.

    Article  Google Scholar 

  • Neilson IR, Yazbeck S. Ultrashort Hirschsprung’s disease: myth or reality. J Pediatr Surg. 1990;25:1135–8.

    Article  CAS  PubMed  Google Scholar 

  • Oue T, Puri P. Altered intramuscular innervation and synapse formation in internal sphincter achalasia. Pediatr Surg Int. 1999;15:192–4.

    Article  CAS  PubMed  Google Scholar 

  • Penman DG, Lilford RJ. The megacystis-microcolon-intestinal hypoperistalsis syndrome: a fatal autosomal recessive condition. J Med Genet. 1989;26:66–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pini Prato A, Rossi V, Fiore M, et al. Megacystis, megacolon, and malrotation: a new syndromic association? Am J Med Genet A. 2011;155A:1798–802. doi:10.1002/ajmg.a.34119.

    Article  CAS  PubMed  Google Scholar 

  • Piotrowska AP, Solari V, Puri P. Distribution of interstitial cells of Cajal in the internal anal sphincter of patients with internal anal sphincter achalasia and Hirschsprung disease. Arch Pathol Lab Med. 2003;127:1192–5. doi:10.1043/1543-2165(2003)127<1192:DOICOC>2.0.CO;2.

    PubMed  Google Scholar 

  • Puri P. Intestinal dysganglionosis and other disorders of intestinal motility. In: Coran AG, Adzick NS, Krummel TM, et al., editors. Pediatric surgery. 7th ed. Philadelphia: Elsevier Saunders; 2012. p. 1279–87.

    Chapter  Google Scholar 

  • Puri P, Fujimoto T. Diagnosis of allied functional bowel disorders using monoclonal antibodies and electronmicroscopy. J Pediatr Surg. 1988;23:546–54.

    Article  CAS  PubMed  Google Scholar 

  • Puri P, Gosemann J-H. Megacystis microcolon intestinal hypoperistalsis syndrome. In: Puri P, editor. Newborn surgery. 3rd ed. London: Hodder Arnold; 2011. p. 615–20.

    Chapter  Google Scholar 

  • Puri P, Gosemann J-H. Variants of Hirschsprung disease. Semin Pediatr Surg. 2012;21:310–8. doi:10.1053/j.sempedsurg.2012.07.005.

    Article  PubMed  Google Scholar 

  • Puri P, Lake BD, Nixon HH, et al. Neuronal colonic dysplasia: an unusual association of Hirschsprung’s disease. J Pediatr Surg. 1977;12:681–5.

    Article  CAS  PubMed  Google Scholar 

  • Puri P, Lake BD, Gorman F, et al. Megacystis-microcolon-intestinal hypoperistalsis syndrome: a visceral myopathy. J Pediatr Surg. 1983;18:64–9.

    Article  CAS  PubMed  Google Scholar 

  • Rolle U, O’Briain S, Pearl RH, Puri P. Megacystis-microcolon-intestinal hypoperistalsis syndrome: evidence of intestinal myopathy. Pediatr Surg Int. 2002;18:2–5. doi:10.1007/s003830200001.

    Article  PubMed  Google Scholar 

  • Sacher P, Briner J, Hanimann B. Is neuronal intestinal dysplasia (NID) a primary disease or a secondary phenomenon? Eur J Pediatr Surg. 1993;3:228–30. doi:10.1055/s-2008-1063549.

    Article  CAS  PubMed  Google Scholar 

  • Schäppi MG, Staiano A, Milla PJ, et al. A practical guide for the diagnosis of primary enteric nervous system disorders. J Pediatr Gastroenterol Nutr. 2013;57:677–86. doi:10.1097/MPG.0b013e3182a8bb50.

    Article  PubMed  Google Scholar 

  • Shirasawa S, Yunker AM, Roth KA, et al. Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon. Nat Med. 1997;3:646–50.

    Article  CAS  PubMed  Google Scholar 

  • Swaminathan M, Kapur RP. Counting myenteric ganglion cells in histologic sections: an empirical approach. Hum Pathol. 2010;41:1097–108. doi:10.1016/j.humpath.2009.12.012.

    Article  PubMed  Google Scholar 

  • Ure BM, Holschneider AM, Schulten D, Meier-Ruge W. Clinical impact of intestinal neuronal malformations: a prospective study in 141 patients. Pediatr Surg Int. 1997;12:377–82.

    Article  CAS  PubMed  Google Scholar 

  • von Boyen GB, Krammer HJ, Suss A, et al. Abnormalities of the enteric nervous system in heterozygous endothelin B receptor deficient (spotting lethal) rats resembling intestinal neuronal dysplasia. Gut. 2002;51:414–9.

    Article  Google Scholar 

  • Wester T, O’Briain DS, Puri P. Notable postnatal alterations in the myenteric plexus of normal human bowel. Gut. 1999;44:666–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young ID, McKeever PA, Brown LA, Lang GD. Prenatal diagnosis of the megacystis-microcolon-intestinal hypoperistalsis syndrome. J Med Genet. 1989;26:403–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang HY, Feng JX, Huang L, et al. Diagnosis and surgical treatment of isolated hypoganglionosis. World J Pediatr. 2008;4:295–300. doi:10.1007/s12519-008-0053-3.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland

    Prem Puri

  2. School of Medicine and Medical Science and Conway Institute of Biomedical Research, University College Dublin, Crumlin, Dublin 12, Ireland

    Prem Puri

  3. Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany

    Jan-Hendrik Gosemann

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  1. Prem Puri
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Correspondence to Prem Puri .

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  1. Our Lady’s Children's Hospital, National Children’s Research Centre, Dublin, Ireland

    Prem Puri

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Puri, P., Gosemann, JH. (2017). Variants of Hirschsprung Disease. In: Puri, P. (eds) Pediatric Surgery. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38482-0_75-1

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  1. Latest

    Variants of Hirschsprung Disease
    Published:
    25 April 2019

    DOI: https://doi.org/10.1007/978-3-642-38482-0_75-2

  2. Original

    Variants of Hirschsprung Disease
    Published:
    29 April 2017

    DOI: https://doi.org/10.1007/978-3-642-38482-0_75-1

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