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Classification and diagnostic criteria of variants of Hirschsprung’s disease

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Abstract

“Variants of Hirschsprung’s disease” are conditions that clinically resemble Hirschsprung’s disease (HD), despite the presence of ganglion cells in rectal suction biopsies. The diagnosis and management of these patients can be challenging. Specific histological, immunohistochemical and electron microscopic investigations are required to characterize this heterogeneous group of functional bowel disorders. Variants of HD include intestinal neuronal dysplasia, intestinal ganglioneuromatosis, isolated hypoganglionosis, immature ganglia, absence of the argyrophil plexus, internal anal sphincter achalasia and congenital smooth muscle cell disorders such as megacystis microcolon intestinal hypoperistalsis syndrome. This review article systematically classifies variants of HD based on current diagnostic criteria with an additional focus on pathogenesis, epidemiology, clinical presentation, management and outcome.

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References

  1. Puri P (1997) Variant Hirschsprung’s disease. J Pediatr Surg 32(2):149–157

    PubMed  CAS  Google Scholar 

  2. Puri P, Rolle U (2004) Variant Hirschsprung’s disease. Semin Pediatr Surg 13(4):293–299

    PubMed  Google Scholar 

  3. Holschneider AM, Meier-Ruge W, Ure BM (1994) Hirschsprung’s disease and allied disorders: a review. Eur J Pediatr Surg 4(5):260–266

    PubMed  CAS  Google Scholar 

  4. Schärli AF (1995) Standardization of terminology of dysganglionoses. Pediatr Surg Int 10(7):440

    Google Scholar 

  5. Meier-Ruge W (1971) Casuistic of colon disorder with symptoms of Hirschsprung’s disease. Verh Dtsch Ges Pathol 55:506–510

    PubMed  CAS  Google Scholar 

  6. Puri P, Lake BD, Nixon HH et al (1977) Neuronal colonic dysplasia: an unusual association of Hirschsprung’s disease. J Pediatr Surg 12(5):681–685

    PubMed  CAS  Google Scholar 

  7. Fadda B, Maier WA, Meier-Ruge W et al (1983) Neuronal intestinal dysplasia. Critical 10-years’ analysis of clinical and biopsy diagnosis. Z Kinderchir 38(5):305–311

    PubMed  CAS  Google Scholar 

  8. Lake BD (1995) Intestinal neuronal dysplasia. Why does it only occur in parts of Europe? Virchows Arch 426(6):537–539

    PubMed  CAS  Google Scholar 

  9. Lumb PD, Moore L (1998) Back to the drawing board. Intestinal neuronal dysplasia type B: not a histological entity yet. Virchows Arch 432(2):99–102

    PubMed  CAS  Google Scholar 

  10. Sacher P, Briner J, Hanimann B (1993) Is neuronal intestinal dysplasia (NID) a primary disease or a secondary phenomenon? Eur J Pediatr Surg 3(4):228–230

    PubMed  CAS  Google Scholar 

  11. Martucciello G, Pini Prato A, Puri P et al (2005) 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. J Pediatr Surg 40(10):1527–1531

    PubMed  Google Scholar 

  12. Milla PJ, Smith VV (1993) Intestinal neuronal dysplasia. J Pediatr Gastroenterol Nutr 17(4):356–357

    PubMed  CAS  Google Scholar 

  13. Hirobe S, Doody DP, Ryan DP et al (1992) Ectopic class II major histocompatibility antigens in Hirschsprung’s disease and neuronal intestinal dysplasia. J Pediatr Surg 27(3):357–362

    PubMed  CAS  Google Scholar 

  14. Kobayashi H, Mahomed A, Puri P (1996) Intestinal neuronal dysplasia in twins. J Pediatr Gastroenterol Nutr 22(4):398–401

    PubMed  CAS  Google Scholar 

  15. Moore SW, Kaschula ROC, Cywes S (1993) Familial and genetic-aspects of neuronal intestinal dysplasia and Hirschsprungs disease. Pediatr Surg Int 8(5):406–409

    Google Scholar 

  16. Hatano M, Aoki T, Dezawa M et al (1997) A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice. J Clin Invest 100(4):795–801

    PubMed  CAS  Google Scholar 

  17. Shirasawa S, Yunker AM, Roth KA et al (1997) Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon. Nat Med 3(6):646–650

    PubMed  CAS  Google Scholar 

  18. von Boyen GB, Krammer HJ, Suss A et al (2002) Abnormalities of the enteric nervous system in heterozygous endothelin B receptor deficient (spotting lethal) rats resembling intestinal neuronal dysplasia. Gut 51(3):414–419

    Google Scholar 

  19. Gath R, Goessling A, Keller KM et al (2001) Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease. Gut 48(5):671–675

    PubMed  CAS  Google Scholar 

  20. Costa M, Fava M, Seri M et al (2000) Evaluation of the HOX11L1 gene as a candidate for congenital disorders of intestinal innervation. J Med Genet 37(7):E9

    PubMed  CAS  Google Scholar 

  21. Fava M, Borghini S, Cinti R et al (2002) HOX11L1: a promoter study to evaluate possible expression defects in intestinal motility disorders. Int J Mol Med 10(1):101–106

    PubMed  CAS  Google Scholar 

  22. Granero Cendón R, Millan Lopez A, Moya Jimenez MJ et al (2007) Intestinal neuronal dysplasia: association with digestive malformations. Cir Pediatr 20(3):166–168

    PubMed  Google Scholar 

  23. Martucciello G, Caffarena PE, Lerone M et al (1994) Neuronal intestinal dysplasia: clinical experience in Italian patients. Eur J Pediatr Surg 4(5):287–292

    PubMed  CAS  Google Scholar 

  24. Meier-Ruge W (1992) Epidemiology of congenital innervation defects of the distal colon. Virchows Arch A Pathol Anat Histopathol 420(2):171–177

    PubMed  CAS  Google Scholar 

  25. Kobayashi H, Hirakawa H, Surana R et al (1995) Intestinal neuronal dysplasia is a possible cause of persistent bowel symptoms after pull-through operation for Hirschsprung’s disease. J Pediatr Surg 30(2):253–257

    PubMed  CAS  Google Scholar 

  26. Montedonico S, Caceres P, Munoz N et al (2011) Histochemical staining for intestinal dysganglionosis: over 30 years experience with more than 1,500 biopsies. Pediatr Surg Int 27(5):479–486

    PubMed  Google Scholar 

  27. Schmittenbecher PP, Sacher P, Cholewa D et al (1999) Hirschsprung’s disease and intestinal neuronal dysplasia: a frequent association with implications for the postoperative course. Pediatr Surg Int 15(8):553–558

    PubMed  CAS  Google Scholar 

  28. Hanimann B, Inderbitzin D, Briner J et al (1992) Clinical relevance of Hirschsprung-associated neuronal intestinal dysplasia (HANID). Eur J Pediatr Surg 2(3):147–149

    PubMed  CAS  Google Scholar 

  29. Schärli AF (1992) Neuronal intestinal dysplasia. Pediatr Surg Int 7(1):2–7

    Google Scholar 

  30. Ure BM, Holschneider AM, Schulten D et al (1997) Clinical impact of intestinal neuronal malformations: a prospective study in 141 patients. Pediatr Surg Int 12(5–6):377–382

    PubMed  CAS  Google Scholar 

  31. Csury L, Peña A (1995) Intestinal neuronal dysplasia: myth or reality? Literature review. Pediatr Surg Int 10(7):441–446

    Google Scholar 

  32. Schärli AF, Meier-Ruge W (1981) Localized and disseminated forms of neuronal intestinal dysplasia mimicking Hirschsprung’s disease. J Pediatr Surg 16(2):164–170

    PubMed  Google Scholar 

  33. Montedonico S, Acevedo S, Fadda B (2002) Clinical aspects of intestinal neuronal dysplasia. J Pediatr Surg 37(12):1772–1774

    PubMed  Google Scholar 

  34. Puri P, Gosemann JH (2012) Variants of Hirschsprung disease. Semin Pediatr Surg 21(4):310–318

    PubMed  Google Scholar 

  35. Martucciello G, Torre M, Pini Prato A et al (2002) Associated anomalies in intestinal neuronal dysplasia. J Pediatr Surg 37(2):219–223

    PubMed  CAS  Google Scholar 

  36. Pini Prato A, Rossi V, Fiore M et al (2011) Megacystis, megacolon, and malrotation: a new syndromic association? Am J Med Genet A 155A(8):1798–1802

    PubMed  CAS  Google Scholar 

  37. Koletzko S, Jesch I, Faus-Kebetaler T et al (1999) Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome. Gut 44(6):853–861

    PubMed  CAS  Google Scholar 

  38. Lumb PD, Moore L (1998) Are giant ganglia a reliable marker of intestinal neuronal dysplasia type B (IND B)? Virchows Arch 432(2):103–106

    PubMed  CAS  Google Scholar 

  39. Kapur RP (2003) Neuronal dysplasia: a controversial pathological correlate of intestinal pseudo-obstruction. Am J Med Genet A 122A(4):287–293

    PubMed  Google Scholar 

  40. Meier-Ruge WA, Brönnimann PB, Gambazzi F et al (1995) Histopathological criteria for intestinal neuronal dysplasia of the submucosal plexus (type B). Virchows Arch 426(6):549–556

    PubMed  CAS  Google Scholar 

  41. Kobayashi H, Hirakawa H, Puri P (1995) What are the diagnostic criteria for intestinal neuronal dysplasia? Pediatr Surg Int 10(7):459–464

    Google Scholar 

  42. Coerdt W, Michel JS, Rippin G et al (2004) Quantitative morphometric analysis of the submucous plexus in age-related control groups. Virchows Arch 444(3):239–246

    PubMed  Google Scholar 

  43. Smith VV (1993) Intestinal neuronal density in childhood: a baseline for the objective assessment of hypo- and hyperganglionosis. Pediatr Pathol 13(2):225–237

    PubMed  CAS  Google Scholar 

  44. Cord-Udy CL, Smith VV, Ahmed S et al (1997) An evaluation of the role of suction rectal biopsy in the diagnosis of intestinal neuronal dysplasia. J Pediatr Gastroenterol Nutr 24(1):1–6

    PubMed  CAS  Google Scholar 

  45. Meyrat BJ, Laurini RN (2003) Plasticity of the enteric nervous system in patients with intestinal neuronal dysplasia associated with Hirschsprung’s disease: a report of three patients. Pediatr Surg Int 19(11):715–720

    PubMed  CAS  Google Scholar 

  46. Meier-Ruge WA, Bruder E (2005) Pathology of chronic constipation in pediatric and adult coloproctology. Pathobiology 72(1–2):1–102

    PubMed  Google Scholar 

  47. Meier-Ruge WA, Schmid PC, Stoss F (1995) Intestinal neuronal dysplasia and its morphometric evidences. Pediatr Surg Int 10(7):447–453

    Google Scholar 

  48. Meier-Ruge WA, Longo-Bauer CH (1997) Morphometric determination of the methodological criteria for the diagnosis of intestinal neuronal dysplasia (IND B). Pathol Res Pract 193(7):465–469

    PubMed  CAS  Google Scholar 

  49. Krammer HJ, Meier-Ruge W, Sigge W et al (1994) Histopathological features of neuronal intestinal dysplasia of the plexus submucosus in whole mounts revealed by immunohistochemistry for PGP 9.5. Eur J Pediatr Surg 4(6):358–361

    PubMed  CAS  Google Scholar 

  50. Tatekawa Y, Kanehiro H, Kanokogi H et al (2000) The evaluation of meconium disease by distribution of cathepsin D in intestinal ganglion cells. Pediatr Surg Int 16(1–2):53–55

    PubMed  CAS  Google Scholar 

  51. Kobayashi H, Miyano T, Yamataka A et al (1997) Use of synaptophysin polyclonal antibody for the rapid intraoperative immunohistochemical evaluation of functional bowel disorders. J Pediatr Surg 32(1):38–40

    PubMed  CAS  Google Scholar 

  52. Wester T, O’Briain S, Puri P (1998) Morphometric aspects of the submucous plexus in whole-mount preparations of normal human distal colon. J Pediatr Surg 33(4):619–622

    PubMed  CAS  Google Scholar 

  53. Wester T, O’Briain DS, Puri P (1999) Notable postnatal alterations in the myenteric plexus of normal human bowel. Gut 44(5):666–674

    PubMed  CAS  Google Scholar 

  54. Kobayashi H, Hirakawa H, Puri P (1996) Is intestinal neuronal dysplasia a disorder of the neuromuscular junction? J Pediatr Surg 31(4):575–579

    PubMed  CAS  Google Scholar 

  55. Rolle U, Piotrowska AP, Puri P (2003) Abnormal vasculature in intestinal neuronal dysplasia. Pediatr Surg Int 19(5):345–348

    PubMed  Google Scholar 

  56. Rolle U, Piaseczna-Piotrowska A, Puri P (2007) Interstitial cells of Cajal in the normal gut and in intestinal motility disorders of childhood. Pediatr Surg Int 23(12):1139–1152

    PubMed  Google Scholar 

  57. Yamataka A, Ohshiro K, Kobayashi H et al (1997) Intestinal pacemaker C-KIT + cells and synapses in allied Hirschsprung’s disorders. J Pediatr Surg 32(7):1069–1074

    PubMed  CAS  Google Scholar 

  58. O’Donnell AM, Puri P (2011) A role for Pten in paediatric intestinal dysmotility disorders. Pediatr Surg Int 27(5):491–493

    PubMed  Google Scholar 

  59. Bruder E, Meier-Ruge WA (2007) Intestinal neuronal dysplasia type B: how do we understand it today? Pathologe 28(2):137–142

    PubMed  CAS  Google Scholar 

  60. Meier-Ruge WA, Ammann K, Bruder E et al (2004) Updated results on intestinal neuronal dysplasia (IND B). Eur J Pediatr Surg 14(6):384–391

    PubMed  CAS  Google Scholar 

  61. Meier-Ruge WA, Bruder E, Kapur RP (2006) Intestinal neuronal dysplasia type B: one giant ganglion is not good enough. Pediatr Dev Pathol 9(6):444–452

    PubMed  Google Scholar 

  62. Ure BM, Holschneider AM, Meier-Ruge W (1994) Neuronal intestinal malformations: a retro- and prospective study on 203 patients. Eur J Pediatr Surg 4(5):279–286

    PubMed  CAS  Google Scholar 

  63. Puri P, Wester T (1998) Intestinal neuronal dysplasia. Semin Pediatr Surg 7(3):181–186

    PubMed  CAS  Google Scholar 

  64. Stoss F, Meier-Ruge W (1994) Experience with neuronal intestinal dysplasia (NID) in adults. Eur J Pediatr Surg 4(5):298–302

    PubMed  CAS  Google Scholar 

  65. Puri P (2003) Intestinal neuronal dysplasia. Semin Pediatr Surg 12(4):259–264

    PubMed  Google Scholar 

  66. Schmittenbecher PP, Gluck M, Wiebecke B et al (2000) Clinical long-term follow-up results in intestinal neuronal dysplasia (IND). Eur J Pediatr Surg 10(1):17–22

    PubMed  CAS  Google Scholar 

  67. Gillick J, Tazawa H, Puri P (2001) Intestinal neuronal dysplasia: results of treatment in 33 patients. J Pediatr Surg 36(5):777–779

    PubMed  CAS  Google Scholar 

  68. Charagundla SR, Levine MS, Torigian DA et al (2004) Diffuse intestinal ganglioneuromatosis mimicking Crohn’s disease. AJR Am J Roentgenol 182(5):1166–1168

    PubMed  Google Scholar 

  69. Matthews MA, Adler BH, Arnold MA et al (2013) Diffuse intestinal ganglioneuromatosis in a child. J Pediatr Surg 48(5):1129–1133

    PubMed  Google Scholar 

  70. D’Amore ESG, Manivel JC, Pettinato G et al (1991) Intestinal ganglioneuromatosis - mucosal and transmural types: a clinicopathological and immunohistochemical study of 6 cases. Hum Pathol 22(3):276–286

    PubMed  Google Scholar 

  71. Moline J, Eng C (2011) Multiple endocrine neoplasia type 2: an overview. Genet Med 13(9):755–764

    PubMed  CAS  Google Scholar 

  72. Puig I, Champeval D, De Santa Barbara P et al (2009) Deletion of Pten in the mouse enteric nervous system induces ganglioneuromatosis and mimics intestinal pseudoobstruction. J Clin Invest 119(12):3586–3596

    PubMed  CAS  Google Scholar 

  73. O’Riordain DS, Obrien T, Crotty TB et al (1995) Multiple endocrine neoplasia type 2B: more than an endocrine disorder. Surgery 118(6):936–942

    PubMed  Google Scholar 

  74. Dunzendorfer T, Lee VW, Levine S et al (1996) Refractory constipation and megacolon in MEN 2b. Dig Dis Sci 41(11):2233–2237

    PubMed  CAS  Google Scholar 

  75. Carney JA, Go VL, Sizemore GW et al (1976) Alimentary-tract ganglioneuromatosis: a major component of the syndrome of multiple endocrine neoplasia type 2b. N Engl J Med 295(23):1287–1291

    PubMed  CAS  Google Scholar 

  76. de Krijger RR, Brooks A, van der Harst E et al (1998) Constipation as the presenting symptom in de novo multiple endocrine neoplasia type 2B. Pediatrics 102(2 Pt 1):405–408

    PubMed  Google Scholar 

  77. Plenat F, Vignaud JM, Floquet J et al (1984) Intestinal ganglioneuromatosis: histochemical, histoenzymological and ultrastructural study of a case. Ann Pathol 4(2):131–136

    PubMed  CAS  Google Scholar 

  78. de Schryver-Kecskemeti K, Clouse RE, Goldstein MN et al (1983) Intestinal ganglioneuromatosis: a manifestation of overproduction of nerve growth factor? N Engl J Med 308(11):635–639

    Google Scholar 

  79. Smith VV, Eng C, Milla PJ (1999) Intestinal ganglioneuromatosis and multiple endocrine neoplasia type 2B: implications for treatment. Gut 45(1):143–146

    PubMed  CAS  Google Scholar 

  80. Torre M, Martucciello G, Ceccherini I et al (2002) Diagnostic and therapeutic approach to multiple endocrine neoplasia type 2B in pediatric patients. Pediatr Surg Int 18(5–6):378–383

    PubMed  CAS  Google Scholar 

  81. Shekitka KM, Sobin LH (1994) Ganglioneuromas of the gastrointestinal tract: relation to Von Recklinghausen disease and other multiple tumor syndromes. Am J Surg Pathol 18(3):250–257

    PubMed  CAS  Google Scholar 

  82. Yin M, King SK, Hutson JM et al (2006) Multiple endocrine neoplasia type 2B diagnosed on suction rectal biopsy in infancy: a report of 2 cases. Pediatr Dev Pathol 9(1):56–60

    PubMed  Google Scholar 

  83. Sonsino E, Nabarra B, Andrianarison I et al (1979) Histological and ultrastructural study of intestinal ganglioneuromatosis: the multiple endocrine neoplasms type IIb syndrome. Ann Anat Pathol (Paris) 24(1):29–44

    CAS  Google Scholar 

  84. Demos TC, Blonder J, Schey WL et al (1983) Multiple endocrine neoplasia (MEN) syndrome type IIB: gastrointestinal manifestations. AJR Am J Roentgenol 140(1):73–78

    PubMed  CAS  Google Scholar 

  85. Feichter S, Meier-Ruge WA, Bruder E (2009) The histopathology of gastrointestinal motility disorders in children. Semin Pediatr Surg 18(4):206–211

    PubMed  Google Scholar 

  86. Unruh A, Fitze G, Janig U et al (2007) Medullary thyroid carcinoma in a 2-month-old male with multiple endocrine neoplasia 2B and symptoms of pseudo-Hirschsprung disease: a case report. J Pediatr Surg 42(9):1623–1626

    PubMed  Google Scholar 

  87. Cohen MS, Phay JE, Albinson C et al (2002) Gastrointestinal manifestations of multiple endocrine neoplasia type 2. Ann Surg 235 (5):648–654; discussion 654–645

    Google Scholar 

  88. Brauckhoff M, Gimm O, Weiss CL et al (2004) Multiple endocrine neoplasia 2B syndrome due to codon 918 mutation: clinical manifestation and course in early and late onset disease. World J Surg 28(12):1305–1311

    PubMed  Google Scholar 

  89. Kobayashi H, Yamataka A, Lane GJ et al (2002) Pathophysiology of hypoganglionosis. J Pediatr Gastroenterol Nutr 34(2):231–235

    PubMed  Google Scholar 

  90. Taguchi T, Masumoto K, Ieiri S et al (2006) New classification of hypoganglionosis: congenital and acquired hypoganglionosis. J Pediatr Surg 41(12):2046–2051

    PubMed  Google Scholar 

  91. Do MY, Myung SJ, Park HJ et al (2011) Novel classification and pathogenetic analysis of hypoganglionosis and adult-onset Hirschsprung’s disease. Dig Dis Sci 56(6):1818–1827

    PubMed  Google Scholar 

  92. Inoue K, Shimotake T, Tomiyama H et al (2001) Mutational analysis of the RET and GDNF gene in children with hypoganglionosis. Eur J Pediatr Surg 11(2):120–123

    PubMed  CAS  Google Scholar 

  93. Rolle U, Yoneda A, Solari V et al (2002) Abnormalities of C-Kit-positive cellular network in isolated hypoganglionosis. J Pediatr Surg 37(5):709–714

    PubMed  Google Scholar 

  94. Kobayashi H, Hirakawa H, Puri P (1996) Abnormal internal anal sphincter innervation in patients with Hirschsprung’s disease and allied disorders. J Pediatr Surg 31(6):794–799

    PubMed  CAS  Google Scholar 

  95. Kobayashi H, Li Z, Yamataka A et al (2003) Overexpression of neural cell adhesion molecule (NCAM) antigens on intestinal smooth muscles in hypoganglionosis: is hypoganglionosis a disorder of the neuromuscular junction? Pediatr Surg Int 19(3):190–193

    PubMed  Google Scholar 

  96. Dingemann J, Puri P (2010) Isolated hypoganglionosis: systematic review of a rare intestinal innervation defect. Pediatr Surg Int 26(11):1111–1115

    PubMed  Google Scholar 

  97. Zhang HY, Feng JX, Huang L et al (2008) Diagnosis and surgical treatment of isolated hypoganglionosis. World J Pediatr 4(4):295–300

    PubMed  CAS  Google Scholar 

  98. Wedel T, Roblick UJ, Ott V et al (2002) Oligoneuronal hypoganglionosis in patients with idiopathic slow-transit constipation. Dis Colon Rectum 45(1):54–62

    PubMed  CAS  Google Scholar 

  99. Watanabe Y, Ito F, Ando H et al (1999) Morphological investigation of the enteric nervous system in Hirschsprung’s disease and hypoganglionosis using whole-mount colon preparation. J Pediatr Surg 34(3):445–449

    PubMed  CAS  Google Scholar 

  100. Bruder E, Meier-Ruge WA (2007) Hypoganglionosis as a cause of chronic constipation. Pathologe 28(2):131–136

    PubMed  CAS  Google Scholar 

  101. Puri P, Fujimoto T (1988) Diagnosis of allied functional bowel disorders using monoclonal antibodies and electronmicroscopy. J Pediatr Surg 23(6):546–554

    PubMed  CAS  Google Scholar 

  102. Meier-Ruge WA, Brunner LA, Engert J et al (1999) A correlative morphometric and clinical investigation of hypoganglionosis of the colon in children. Eur J Pediatr Surg 9(2):67–74

    PubMed  CAS  Google Scholar 

  103. Kubota A, Yamauchi K, Yonekura T et al (2001) Clinicopathologic relationship of hypoganglionosis. J Pediatr Surg 36(6):898–900

    PubMed  CAS  Google Scholar 

  104. Miyazaki E, Ohshiro K, Puri P (1998) NADPH-diaphorase histochemical staining of suction rectal biopsies in the diagnosis of Hirschsprung’s disease and allied disorders. Pediatr Surg Int 13(7):464–467

    PubMed  CAS  Google Scholar 

  105. Yamataka A, Fujiwara T, Nishiye H et al (1996) Localization of intestinal pacemaker cells and synapses in the muscle layers of a patient with colonic hypoganglionosis. J Pediatr Surg 31(4):584–587

    PubMed  CAS  Google Scholar 

  106. Munakata K, Okabe I, Morita K (1992) Hypoganglionosis. Pediatr Surg Int 7(1):8–11

    Google Scholar 

  107. Schärli AF, Sossai R (1998) Hypoganglionosis. Semin Pediatr Surg 7(3):187–191

    PubMed  Google Scholar 

  108. Burki T, Kiho L, Scheimberg I et al (2011) Neonatal functional intestinal obstruction and the presence of severely immature ganglion cells on rectal biopsy: 6 year experience. Pediatr Surg Int 27(5):487–490

    PubMed  Google Scholar 

  109. Smith B (1968) Pre- and postnatal development of the ganglion cells of the rectum and its surgical implications. J Pediatr Surg 3(3):386–391

    PubMed  CAS  Google Scholar 

  110. Montedonico S, Sri Paran T, Pirker M et al (2006) Developmental changes in submucosal nitrergic neurons in the porcine distal colon. J Pediatr Surg 41(5):1029–1035

    PubMed  Google Scholar 

  111. Sri Paran T, Rolle U, Puri P (2006) Postnatal development of the mucosal plexus in the porcine small and large intestine. Pediatr Surg Int 22(12):997–1001

    Google Scholar 

  112. Sri Paran T, Rolle U, Puri P (2008) Postnatal changes in enteric plexus axonal thickness. Pediatr Surg Int 24(12):1365–1367

    PubMed  Google Scholar 

  113. Bughaighis AG, Emergy JL (1971) Functional obstruction of the intestine due to neurological immaturity. Prog Pediatr Surg 3:37–52

    PubMed  CAS  Google Scholar 

  114. Venugopal S, Mancer K, Shandling B (1981) The validity of rectal biopsy in relation to morphology and distribution of ganglion cells. J Pediatr Surg 16(4):433–437

    PubMed  CAS  Google Scholar 

  115. Park SH, Min H, Chi JG et al (2005) Immunohistochemical studies of pediatric intestinal pseudo-obstruction: bcl2, a valuable biomarker to detect immature enteric ganglion cells. Am J Surg Pathol 29(8):1017–1024

    PubMed  Google Scholar 

  116. Tanner MS, Smith B, Lloyd JK (1976) Functional intestinal obstruction due to deficiency of argyrophil neurones in the myenteric plexus: familial syndrome presenting with short small bowel, malrotation, and pyloric hypertrophy. Arch Dis Child 51(11):837–841

    PubMed  CAS  Google Scholar 

  117. Singh I (1963) The prenatal development of enterochromaffin cells in the human gastro-intestinal tract. J Anat 97:377–387

    PubMed  CAS  Google Scholar 

  118. Lolova IS, Davidoff MS, Itzev DE (1998) Histological and immunocytochemical data on the differentiation of intestinal endocrine cells in human fetus. Acta Physiol Pharmacol Bulg 23(3–4):61–71

    PubMed  CAS  Google Scholar 

  119. Auricchio A, Brancolini V, Casari G et al (1996) The locus for a novel syndromic form of neuronal intestinal pseudoobstruction maps to Xq28. Am J Hum Genet 58(4):743–748

    PubMed  CAS  Google Scholar 

  120. Puri P, Lake BD, Nixon HH (1977) Adynamic bowel syndrome: report of a case with disturbance of the cholinergic innervation. Gut 18(9):754–759

    PubMed  CAS  Google Scholar 

  121. Garvey W, Fathi A, Bigelow F et al (1989) A new method for demonstrating argyrophil cells of the pancreas and intestines. Stain Technol 64(2):87–91

    PubMed  CAS  Google Scholar 

  122. Bentley JF (1978) Faecal soiling and anal achalasia. Arch Dis Child 53(3):185–186

    PubMed  CAS  Google Scholar 

  123. Fadda B, Welskop J, Müntefering H et al (1987) Achalasia of the anal sphincter. Pediatr Surg Int 2(2):81–85

    Google Scholar 

  124. Davidson M, Bauer CH (1958) Studies of distal colonic motility in children. IV. Achalasia of the distal rectal segment despite presence of ganglia in the myenteric plexuses of this area. Pediatrics 21(5):746–761

    PubMed  CAS  Google Scholar 

  125. de Caluwé D, Yoneda A, Akl U et al (2001) Internal anal sphincter achalasia: outcome after internal sphincter myectomy. J Pediatr Surg 36(5):736–738

    PubMed  Google Scholar 

  126. Doodnath R, Puri P (2009) Internal anal sphincter achalasia. Semin Pediatr Surg 18(4):246–248

    PubMed  Google Scholar 

  127. Lake BD, Puri P, Nixon HH et al (1978) Hirschsprung’s disease: an appraisal of histochemically demonstrated acetylcholinesterase activity in suction rectal biopsy specimens as an aid to diagnosis. Arch Pathol Lab Med 102(5):244–247

    PubMed  CAS  Google Scholar 

  128. Neilson IR, Yazbeck S (1990) Ultrashort Hirschsprung’s disease: myth or reality. J Pediatr Surg 25(11):1135–1138

    PubMed  CAS  Google Scholar 

  129. Fujimoto T, Puri P, Miyano T (1992) Abnormal peptidergic innervation in internal sphincter achalasia. Pediatr Surg Int 7(1):12–17

    Google Scholar 

  130. Hirakawa H, Kobayashi H, O’Briain DS et al (1995) Absence of NADPH-diaphorase activity in internal anal sphincter (IAS) achalasia. J Pediatr Gastroenterol Nutr 20(1):54–58

    PubMed  CAS  Google Scholar 

  131. Oue T, Puri P (1999) Altered intramuscular innervation and synapse formation in internal sphincter achalasia. Pediatr Surg Int 15(3–4):192–194

    PubMed  CAS  Google Scholar 

  132. Piotrowska AP, Solari V, Puri P (2003) 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 127(9):1192–1195

    PubMed  Google Scholar 

  133. de Lorijn F, de Jonge WJ, Wedel T et al (2005) Interstitial cells of Cajal are involved in the afferent limb of the rectoanal inhibitory reflex. Gut 54(8):1107–1113

    PubMed  Google Scholar 

  134. Friedmacher F, Puri P (2012) 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 28(8):765–771

    PubMed  Google Scholar 

  135. Doodnath R, Puri P (2009) Long-term outcome of internal sphincter myectomy in patients with internal anal sphincter achalasia. Pediatr Surg Int 25(10):869–871

    PubMed  Google Scholar 

  136. Hecker WC, Holschneider A, Fendel H et al (1973) Chronic constipation in children due to achalasia of the internal anal sphincter. Dtsch Med Wochenschr 98(49):2334–2340

    PubMed  CAS  Google Scholar 

  137. Heikkinen M, Lindahl H, Rintala RJ (2005) Long-term outcome after internal sphincter myectomy for internal sphincter achalasia. Pediatr Surg Int 21(2):84–87

    PubMed  CAS  Google Scholar 

  138. Ciamarra P, Nurko S, Barksdale E et al (2003) Internal anal sphincter achalasia in children: clinical characteristics and treatment with Clostridium botulinum toxin. J Pediatr Gastroenterol Nutr 37(3):315–319

    PubMed  CAS  Google Scholar 

  139. Irani K, Rodriguez L, Doody DP et al (2008) Botulinum toxin for the treatment of chronic constipation in children with internal anal sphincter dysfunction. Pediatr Surg Int 24(7):779–783

    PubMed  Google Scholar 

  140. Koivusalo AI, Pakarinen MP, Rintala RJ (2009) Botox injection treatment for anal outlet obstruction in patients with internal anal sphincter achalasia and Hirschsprung’s disease. Pediatr Surg Int 25(10):873–876

    PubMed  CAS  Google Scholar 

  141. Langer JC, Birnbaum E (1997) Preliminary experience with intrasphincteric botulinum toxin for persistent constipation after pull-through for Hirschsprung’s disease. J Pediatr Surg 32(7):1059–1061

    PubMed  CAS  Google Scholar 

  142. Messineo A, Codrich D, Monai M et al (2001) The treatment of internal anal sphincter achalasia with botulinum toxin. Pediatr Surg Int 17(7):521–523

    PubMed  CAS  Google Scholar 

  143. Minkes RK, Langer JC (2000) A prospective study of botulinum toxin for internal anal sphincter hypertonicity in children with Hirschsprung’s disease. J Pediatr Surg 35(12):1733–1736

    PubMed  CAS  Google Scholar 

  144. Boman F, Sfeir R, Bonnevalle M et al (2006) Complexity of pathological interpretation in megacystis-microcolon-intestinal hypoperistalsis syndrome. Ann Pathol 26(2):115–121

    PubMed  Google Scholar 

  145. Berdon WE, Baker DH, Blanc WA et al (1976) 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 126(5):957–964

    PubMed  CAS  Google Scholar 

  146. Chamyan G, Debich-Spicer D, Opitz JM et al (2001) Megacystis-microcolon-intestinal hypoperistalsis syndrome and aganglionosis in trisomy 18. Am J Med Genet 102(3):293–296

    PubMed  CAS  Google Scholar 

  147. Ciftci AO, Cook RC, van Velzen D (1996) Megacystis microcolon intestinal hypoperistalsis syndrome: evidence of a primary myocellular defect of contractile fiber synthesis. J Pediatr Surg 31(12):1706–1711

    PubMed  CAS  Google Scholar 

  148. Puri P, Tsuji M (1992) Megacystis-microcolon-intestinal hypoperistalsis syndrome (neonatal hollow visceral myopathy). Pediatr Surg Int 7(1):18–22

    Google Scholar 

  149. Rolle U, O’Briain S, Pearl RH et al (2002) Megacystis-microcolon-intestinal hypoperistalsis syndrome: evidence of intestinal myopathy. Pediatr Surg Int 18(1):2–5

    PubMed  Google Scholar 

  150. Gillis DA, Grantmyre EB (1985) Megacystis-microcolon-intestinal hypoperistalsis syndrome: survival of a male infant. J Pediatr Surg 20(3):279–281

    PubMed  CAS  Google Scholar 

  151. Taguchi T, Ikeda K, Shono T et al (1989) Autonomic innervation of the intestine from a baby with megacystis microcolon intestinal hypoperistalsis syndrome: immunohistochemical study. J Pediatr Surg 24(12):1264–1266

    PubMed  CAS  Google Scholar 

  152. Srikanth MS, Ford EG, Isaacs H Jr et al (1993) Megacystis microcolon intestinal hypoperistalsis syndrome: late sequelae and possible pathogenesis. J Pediatr Surg 28(7):957–959

    PubMed  CAS  Google Scholar 

  153. Xu W, Gelber S, Orr-Urtreger A et al (1999) Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 96(10):5746–5751

    PubMed  CAS  Google Scholar 

  154. Richardson CE, Morgan JM, Jasani B et al (2001) Megacystis-microcolon-intestinal hypoperistalsis syndrome and the absence of the alpha3 nicotinic acetylcholine receptor subunit. Gastroenterology 121(2):350–357

    PubMed  CAS  Google Scholar 

  155. Xu W, Orr-Urtreger A, Nigro F et al (1999) Multiorgan autonomic dysfunction in mice lacking the beta2 and the beta4 subunits of neuronal nicotinic acetylcholine receptors. J Neurosci 19(21):9298–9305

    PubMed  CAS  Google Scholar 

  156. Lev-Lehman E, Bercovich D, Xu W et al (2001) Characterization of the human beta4 nAChR gene and polymorphisms in CHRNA3 and CHRNB4. J Hum Genet 46(7):362–366

    PubMed  CAS  Google Scholar 

  157. Puri P, Lake BD, Gorman F et al (1983) Megacystis-microcolon-intestinal hypoperistalsis syndrome: a visceral myopathy. J Pediatr Surg 18(1):64–69

    PubMed  CAS  Google Scholar 

  158. Schuffler MD, Pagon RA, Schwartz R et al (1988) Visceral myopathy of the gastrointestinal and genitourinary tracts in infants. Gastroenterology 94(4):892–898

    PubMed  CAS  Google Scholar 

  159. Piotrowska AP, Rolle U, Chertin B et al (2003) Alterations in smooth muscle contractile and cytoskeleton proteins and interstitial cells of Cajal in megacystis microcolon intestinal hypoperistalsis syndrome. J Pediatr Surg 38(5):749–755

    PubMed  Google Scholar 

  160. Szigeti R, Chumpitazi BP, Finegold MJ et al (2010) Absent smooth muscle actin immunoreactivity of the small bowel muscularis propria circular layer in association with chromosome 15q11 deletion in megacystis-microcolon-intestinal hypoperistalsis syndrome. Pediatr Dev Pathol 13(4):322–325

    PubMed  Google Scholar 

  161. Masetti M, Rodriguez MM, Thompson JF et al (1999) Multivisceral transplantation for megacystis microcolon intestinal hypoperistalsis syndrome. Transplantation 68(2):228–232

    PubMed  CAS  Google Scholar 

  162. Piaseczna Piotrowska A, Rolle U, Solari V et al (2004) Interstitial cells of Cajal in the human normal urinary bladder and in the bladder of patients with megacystis-microcolon intestinal hypoperistalsis syndrome. BJU Int 94(1):143–146

    PubMed  Google Scholar 

  163. Kirtane J, Talwalker V, Dastur DK (1984) Megacystis, microcolon, intestinal hypoperistalsis syndrome: possible pathogenesis. J Pediatr Surg 19(2):206–208

    PubMed  CAS  Google Scholar 

  164. al-Rayess M, Ambler MW (1992) Axonal dystrophy presenting as the megacystis-microcolon-intestinal hypoperistalsis syndrome. Pediatr Pathol 12(5):743–750

    Google Scholar 

  165. Gosemann JH, Puri P (2011) Megacystis microcolon intestinal hypoperistalsis syndrome: systematic review of outcome. Pediatr Surg Int 27(10):1041–1046

    PubMed  Google Scholar 

  166. Köhler M, Pease PW, Upadhyay V (2004) Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in siblings: case report and review of the literature. Eur J Pediatr Surg 14(5):362–367

    PubMed  Google Scholar 

  167. Young ID, McKeever PA, Brown LA et al (1989) Prenatal diagnosis of the megacystis-microcolon-intestinal hypoperistalsis syndrome. J Med Genet 26(6):403–406

    PubMed  CAS  Google Scholar 

  168. Mc Laughlin D, Puri P (2013) Familial megacystis microcolon intestinal hypoperistalsis syndrome: a systematic review. Pediatr Surg Int (in press)

  169. McNamara HM, Onwude JL, Thornton JG (1994) Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report supporting autosomal recessive inheritance. Prenat Diagn 14(2):153–154

    PubMed  CAS  Google Scholar 

  170. Penman DG, Lilford RJ (1989) The megacystis-microcolon-intestinal hypoperistalsis syndrome: a fatal autosomal recessive condition. J Med Genet 26(1):66–67

    PubMed  CAS  Google Scholar 

  171. Rolle U, Puri P (2006) Structural basis of voiding dysfunction in megacystis microcolon intestinal hypoperistalsis syndrome. J Pediatr Urol 2(4):277–284

    PubMed  Google Scholar 

  172. Granata C, Puri P (1997) Megacystis-microcolon-intestinal hypoperistalsis syndrome. J Pediatr Gastroenterol Nutr 25(1):12–19

    PubMed  CAS  Google Scholar 

  173. Garel C, Dreux S, Philippe-Chomette P et al (2006) Contribution of fetal magnetic resonance imaging and amniotic fluid digestive enzyme assays to the evaluation of gastrointestinal tract abnormalities. Ultrasound Obstet Gynecol 28(3):282–291

    PubMed  CAS  Google Scholar 

  174. Puri P, Shinkai M (2005) Megacystis microcolon intestinal hypoperistalsis syndrome. Semin Pediatr Surg 14(1):58–63

    PubMed  Google Scholar 

  175. Loinaz C, Rodriguez MM, Kato T et al (2005) Intestinal and multivisceral transplantation in children with severe gastrointestinal dysmotility. J Pediatr Surg 40(10):1598–1604

    PubMed  Google Scholar 

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

    Florian Friedmacher & Prem Puri

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

    Prem Puri

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  1. Florian Friedmacher
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Correspondence to Prem Puri.

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Friedmacher, F., Puri, P. Classification and diagnostic criteria of variants of Hirschsprung’s disease. Pediatr Surg Int 29, 855–872 (2013). https://doi.org/10.1007/s00383-013-3351-3

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