• Masayuki KubotaEmail author


The typical symptomatic presentations of Hirschsprung’s disease (HD) are a delayed passage of meconium and abdominal distension with bilious vomiting. The characteristics of HD patients are male predominance of 3–4:1 and full-term neonates weighing more than 2500 g. In term neonates, the passage of meconium is usually observed within 24 h of birth. Therefore, a delayed passage of meconium is an important presenting sign of HD in term neonates. However, this phenomenon is frequently found in other clinical conditions, such as preterm infants, chronic constipation, meconium ileus, and congenital small intestinal obstruction. Even though the association of HD in preterm infants is infrequent (5%), a careful diagnostic work-up is necessary to exclude HD in preterm neonates. A majority of HD patients are diagnosed in the neonatal and early infantile period. However, a certain population of HD patients are diagnosed after the infantile period. Furthermore, there are cases that first present with signs of enterocolitis, toxic megacolon, and intestinal perforation. This symptomatic diversity necessitates careful attention in the diagnosis of HD. In cases of total colonic aganglionosis, a tendency toward a later-than-expected diagnosis is observed, probably due to the different genetic background from that of short-segment HD. An association with Down syndrome is frequent in HD, and this association is likely to worsen the pre- and post-operative clinical presentations. Food allergy and congenital hypothyroidism necessitate careful attention for the differential diagnosis of HD in the neonatal period.


Delayed passage of meconium Abdominal distension Bilious vomiting Down syndrome Enterocolitis 


  1. 1.
    Taguchi T, Obata S, Ieiri S. Current status of Hirschsprung’s disease: based on a nationwide survey of Japan. Pediatr Surg Int. 2017;33(4):497–504.CrossRefGoogle Scholar
  2. 2.
    Best KE, Addor MC, Arriola L, Balku E, Barisic I, Bianchi F, et al. Hirschsprung’s disease prevalence in Europe: a register based study. Birth Defects Res A Clin Mol Teratol. 2014;100(9):695–702.CrossRefGoogle Scholar
  3. 3.
    Garver KL, Law JC, Garver B. Hirschsprung disease: a genetic study. Clin Genet. 1985;28(6):503–8.CrossRefGoogle Scholar
  4. 4.
    Goldberg EL. An epidemiological study of Hirschsprung’s disease. Int J Epidemiol. 1984;13(4):479–85.CrossRefGoogle Scholar
  5. 5.
    Taguchi T, Ieiri S, Miyoshi K, Kohashi K, Oda Y, Kubota A, et al. The incidence and outcome of allied disorders of Hirschsprung’s disease in Japan: results from a nationwide survey. Asian J Surg. 2017;40(1):29–34.CrossRefGoogle Scholar
  6. 6.
    Zweier C, Albrecht B, Mitulla B, Behrens R, Beese M, Gillessen-Kaesbach G, et al. “Mowat-Wilson” syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene. Am J Med Genet. 2002;108(3):177–81.CrossRefGoogle Scholar
  7. 7.
    Alkuraya FS, Lin AE, Irons MB, Kimonis VE. Fryns syndrome with Hirschsprung disease: support for possible neural crest involvement. Am J Med Genet A. 2005;132A(2):226–30.CrossRefGoogle Scholar
  8. 8.
    Islek I, Kucukoduk S, Erkan D, Bernay F, Kalayci AG, Gork S, et al. Bardet-Biedl syndrome: delayed diagnosis in a child with Hirschsprung disease. Clin Dysmorphol. 1996;5(3):271–3.CrossRefGoogle Scholar
  9. 9.
    Yomo A, Taira T, Kondo I. Goldberg-Shprintzen syndrome: Hirschsprung disease, hypotonia, and ptosis in sibs. Am J Med Genet. 1991;41(2):188–91.CrossRefGoogle Scholar
  10. 10.
    Pini Prato A, Musso M, Ceccherini I, Mattioli G, Giunta C, Ghiggeri GM, et al. Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association. Medicine (Baltimore). 2009;88(2):83–90.CrossRefGoogle Scholar
  11. 11.
    Ogala WN, Amiebenomo CS. The time of passage of the first urine and stool by Nigerian neonates. Trop Geogr Med. 1986;38(4):415–7.PubMedGoogle Scholar
  12. 12.
    Okoro PE, Enyindah CE. Time of passage of First Stool in Newborns in a Tertiary Health Facility in Southern Nigeria. Niger J Surg. 2013;19(1):20–2.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Gulcan H, Gungor S, Tiker F, Kilicdag H. Effect of perinatal factors on time of first stool passage in preterm newborns: An open, prospective study. Curr Ther Res Clin Exp. 2006;67(3):214–25.CrossRefGoogle Scholar
  14. 14.
    Weaver LT, Lucas A. Development of bowel habit in preterm infants. Arch Dis Child. 1993;68(3 Spec No):317–20.Google Scholar
  15. 15.
    Dimmitt RA, Moss RL. Meconium diseases in infants with very low birth weight. Semin Pediatr Surg. 2000;9(2):79–83.CrossRefGoogle Scholar
  16. 16.
    Swenson O, Sherman JO, Fisher JH. Diagnosis of congenital megacolon: an analysis of 501 patients. J Pediatr Surg. 1973;8(5):587–94.CrossRefGoogle Scholar
  17. 17.
    Singh SJ, Croaker GD, Manglick P, Wong CL, Athanasakos H, Elliott E, et al. Hirschsprung’s disease: the Australian Paediatric Surveillance Unit’s experience. Pediatr Surg Int. 2003;19(4):247–50.CrossRefGoogle Scholar
  18. 18.
    Bradnock TJ, Knight M, Kenny S, Nair M, Walker GM. British Association of Paediatric Surgeons Congenital Anomalies Surveillance S. Hirschsprung’s disease in the UK and Ireland: incidence and anomalies. Arch Dis Child. 2017;102(8):722–7.CrossRefGoogle Scholar
  19. 19.
    de Lorijn F, Boeckxstaens GE, Benninga MA. Symptomatology, pathophysiology, diagnostic work-up, and treatment of Hirschsprung disease in infancy and childhood. Curr Gastroenterol Rep. 2007;9(3):245–53.CrossRefGoogle Scholar
  20. 20.
    Alehossein M, Roohi A, Pourgholami M, Mollaeian M, Salamati P. Diagnostic accuracy of radiologic scoring system for evaluation of suspicious Hirschsprung disease in children. Iran J Radiol. 2015;12(2):e12451.CrossRefGoogle Scholar
  21. 21.
    Klein MD, Coran AG, Wesley JR, Drongowski RA. Hirschsprung’s disease in the newborn. J Pediatr Surg. 1984;19(4):370–4.CrossRefGoogle Scholar
  22. 22.
    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(5):588–97.CrossRefGoogle Scholar
  23. 23.
    Cheng S, Wang J, Pan W, Yan W, Shi J, Guan W, et al. Pathologically assessed grade of Hirschsprung-associated enterocolitis in resected colon in children with Hirschsprung’s disease predicts postoperative bowel function. J Pediatr Surg. 2017;52(11):1776–81.CrossRefGoogle Scholar
  24. 24.
    Imamura A, Puri P, O’Briain DS, Reen DJ. Mucosal immune defence mechanisms in enterocolitis complicating Hirschsprung’s disease. Gut. 1992;33(6):801–6.CrossRefGoogle Scholar
  25. 25.
    Rescorla FJ, Morrison AM, Engles D, West KW, Grosfeld JL. Hirschsprung’s disease. Evaluation of mortality and long-term function in 260 cases. Arch Surg. 1992;127(8):934–41.. discussion 941–2CrossRefGoogle Scholar
  26. 26.
    Peres LC, Cohen MC. Sudden unexpected early neonatal death due to undiagnosed Hirschsprung disease enterocolitis: a report of two cases and literature review. Forensic Sci Med Pathol. 2013;9(4):558–63.CrossRefGoogle Scholar
  27. 27.
    Garg SR, Sathe PA, Taware AC, Surve KM. Fatal toxic megacolon in a child of Hirschsprung disease. J Clin Diagn Res. 2016;10(12):ED03–5.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Khan AM, Murty TV. Enteric perforation in a newborn with Hirschsprung’s disease. Indian Pediatr. 1973;10(7):453–4.PubMedGoogle Scholar
  29. 29.
    Han SB, Kim J, Moon SB. Jejunal perforation as an unusual presentation of total colonic aganglionosis in a neonate: a case report. Int J Surg Case Rep. 2017;41:117–20.CrossRefGoogle Scholar
  30. 30.
    Ajayi OO, Solanke TF, Seriki O, Bohrer SP. Hirschsprung’s disease in the neonate presenting as cecal perforation. Pediatrics. 1969;43(1):102–6.PubMedGoogle Scholar
  31. 31.
    Morsi AH, Omar HR, Osama A, Khodary AR. Clinical spectrum of neonates presenting with pneumoperitoneum: a retrospective study. Afr J Paediatr Surg. 2016;13(3):120–4.CrossRefGoogle Scholar
  32. 32.
    Hsieh WS, Yang PH, Huang CS, Wang CR. Hirschsprung’s disease presenting with diffuse intestinal pneumatosis in a neonate. Acta Paediatr Taiwan. 2000;41(6):336–8.PubMedGoogle Scholar
  33. 33.
    Zeng M, Amodio J, Schwarz S, Garrow E, Xu J, Rabinowitz SS. Hirschsprung disease presenting as sigmoid volvulus: a case report and review of the literature. J Pediatr Surg. 2013;48(1):243–6.CrossRefGoogle Scholar
  34. 34.
    Kenny SE, Vanderwinden JM, Rintala RJ, Connell MG, Lloyd DA, Vanderhaegen JJ, et al. Delayed maturation of the interstitial cells of Cajal: a new diagnosis for transient neonatal pseudoobstruction. Report of two cases. J Pediatr Surg. 1998;33(1):94–8.CrossRefGoogle Scholar
  35. 35.
    Yoo SY, Jung SH, Eom M, Kim IH, Han A. Delayed maturation of interstitial cells of Cajal in meconium obstruction. J Pediatr Surg. 2002;37(12):1758–61.CrossRefGoogle Scholar
  36. 36.
    Sharp NE, Pettiford-Cunningham J, Shah SR, Thomas P, Juang D, St Peter SD, et al. The prevalence of Hirschsprung disease in premature infants after suction rectal biopsy. J Surg Res. 2013;184(1):374–7.CrossRefGoogle Scholar
  37. 37.
    Ikeda K, Goto S. Total colonic aganglionosis with or without small bowel involvement: an analysis of 137 patients. J Pediatr Surg. 1986;21(4):319–22.CrossRefGoogle Scholar
  38. 38.
    Anupama B, Zheng S, Xiao X. Ten-year experience in the management of total colonic aganglionosis. J Pediatr Surg. 2007;42(10):1671–6.CrossRefGoogle Scholar
  39. 39.
    Lall A, Agarwala S, Bhatnagar V, Gupta AK, Mitra DK. Total colonic aganglionosis: diagnosis and management in a 12-year-old boy. J Pediatr Surg. 1999;34(9):1413–4.CrossRefGoogle Scholar
  40. 40.
    Myers MB, Bradburn D, Vela R, Payzant A, Karlin S. Total aganglionic colon in an adult: first reported case. Ann Surg. 1966;163(1):97–102.CrossRefGoogle Scholar
  41. 41.
    Lefebvre MP, Leape LL, Pohl DA, Safaii H, Grand RJ. Total colonic aganglionosis initially diagnosed in an adolescent. Gastroenterology. 1984;87(6):1364–6.CrossRefGoogle Scholar
  42. 42.
    Moore SW. Total colonic aganglionosis in Hirschsprung disease. Semin Pediatr Surg. 2012;21(4):302–9.CrossRefGoogle Scholar
  43. 43.
    Ryan ET, Ecker JL, Christakis NA, Folkman J. Hirschsprung’s disease: associated abnormalities and demography. J Pediatr Surg. 1992;27(1):76–81.CrossRefGoogle Scholar
  44. 44.
    Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet. 1990;46(3):568–80.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Friedmacher F, Puri P. Hirschsprung’s disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality. Pediatr Surg Int. 2013;29(9):937–46.CrossRefGoogle Scholar
  46. 46.
    Moore SW, Zaahl MG. Intronic RET gene variants in Down syndrome-associated Hirschsprung disease in an African population. J Pediatr Surg. 2012;47(2):299–302.CrossRefGoogle Scholar
  47. 47.
    Hackam DJ, Reblock K, Barksdale EM, Redlinger R, Lynch J, Gaines BA. The influence of Down’s syndrome on the management and outcome of children with Hirschsprung’s disease. J Pediatr Surg. 2003;38(6):946–9.CrossRefGoogle Scholar
  48. 48.
    Menezes M, Pini Prato A, Jasonni V, Puri P. Long-term clinical outcome in patients with total colonic aganglionosis: a 31-year review. J Pediatr Surg. 2008;43(9):1696–9.CrossRefGoogle Scholar
  49. 49.
    Morabito A, Lall A, Gull S, Mohee A, Bianchi A. The impact of Down’s syndrome on the immediate and long-term outcomes of children with Hirschsprung’s disease. Pediatr Surg Int. 2006;22(2):179–81.CrossRefGoogle Scholar
  50. 50.
    Mcllhenny J, Sutphen JL, Block CA. Food allergy presenting as obstruction in an infant. Am J Roentgenol. 1988;150(2):373–5.CrossRefGoogle Scholar
  51. 51.
    Umeda S, Kawahara H, Yoneda A, Tazuke Y, Tani G, Ishii T, et al. Impact of cow’s milk allergy on enterocolitis associated with Hirschsprung’s disease. Pediatr Surg Int. 2013;29(11):1159–63.CrossRefGoogle Scholar
  52. 52.
    Kubota A, Kawahara H, Okuyama H, Shimizu Y, Nakacho M, Ida S, et al. Cow’s milk protein allergy presenting with Hirschsprung’s disease-mimicking symptoms. J Pediatr Surg. 2006;41(12):2056–8.CrossRefGoogle Scholar
  53. 53.
    Sharma D, Murki S, Dhanraj G. Congenital hypothyroidism presenting with seizures and pseudo-Hirschsprung’s disease in newborn. Indian J Pediatr. 2014;81(8):837.CrossRefGoogle Scholar
  54. 54.
    Buyukyilmaz G, Baltu D, Soyer T, Tanyildiz M, Demirbilek H. Severe hyponatremia and repeated intestinal resections for intestinal dysmotility mimicking congenital aganglionic megacolon due to delay in the diagnosis of congenital hypothyroidism. Ann Pediatr Endocrinol Metab. 2016;21(4):230–4.CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Pediatric SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigata CityJapan

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