Novosti
Khirurgii
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Year 2020 Vol. 28 No 1

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DOI: https://dx.doi.org/10.18484/2305-0047.2020.1.84   |  

D.A. MOROZOV, E.S. PIMENOVA, T.D. MARCHUK

HIRSCHSPRUNGS DISEASE IN CHILDREN WITH DOWN SYNDROME. FEATURES OF CLINICAL ASPECTS, DIAGNOSTICS AND TREATMENT

I.M. Sechenov First Moscow State Medical University, Moscow,
The Russian Federation

The purpose of this review was to combine information about children with aganglionosis and Down syndrome and about the possible causes of high complication rates in this group of patients. Down syndrome is the most common chromosomal abnormality associated with Hirschsprungs disease (2-10%). The mortality rate in this group of patients is higher. The cause, in addition to combined congenital heart defects, is a specific complication for aganglionic patients Hirschsprung-associated enterocolitis. The incidence of enterocolitis before and after surgical treatment is statistically significantly higher in children with Down syndrome (29-48%). This may be due to specific disorders in the leukocytes, interferon protection of the intestinal mucosa, as well as blockade of serotonin production and vasoactive intestinal peptide involved in the protection of the enteral nervous system. The frequency of other poor functional results after pull-through surgery (constipation/incontinence) in children with Down syndrome does not statistically different from other patients. Awareness of a physician and parents about the possible risk of developing severe enterocolitis in a child with aganglionosis and Down syndrome can help to choose the treatment and postoperative observation of such patients and to prevent serious complication.

Keywords: congenital malformations, Hirschsprung disease, Down syndrome, hirschsprung-associated enterocolitis, children
p. 84-91 of the original issue
References
  1. Chakravarti A, McCallion AS, Lyonnet S. Part 30: Hirschsprung Disease. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson KM, Mitchell G, editors. P. 251. doi: 10.1036/ommbid.291
  2. Slavikova T, Zabojnikova L, Babala J, Varga I. An embryological point of view on associated congenital anomalies of children with Hirschsprung disease. Bratisl Lek Listy. 2015;116(11):640-47. doi: 10.4149/BLL_2015_126
  3. Amiel J, Lyonnet S. Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet. 2001 Nov;38(11):729-39. doi: 10.1136/jmg.38.11.729
  4. Pini Prato A, Rossi V, Mosconi M, Holm C, Lantieri F, Griseri P, Ceccherini I, Mavilio D, Jasonni V, Tuo G, Derchi M, Marasini M, Magnano G, Granata C, Ghiggeri G, Priolo E, Sposetti L, Porcu A, Buffa P, Mattioli G. A prospective observational study of associated anomalies in Hirschsprungs disease. Orphanet J Rare Dis. 2013 Nov 23;8:184. doi: 10.1186/1750-1172-8-184
  5. Yin H, Boyd T, Pacheco MC, Schonfeld D, Bove KE. Rectal biopsy in children with Down syndrome and chronic constipation: Hirschsprung disease vs non-Hirschsprung disease. Pediatr Dev Pathol. 2012 Mar-Apr;15(2):87-95. doi: 10.2350/11-01-0957-OA.1
  6. Burkardt DD, Graham JM Jr, Short SS, Frykman PK. Advances in Hirschsprung disease genetics and treatment strategies: an update for the primary care pediatrician. Clin Pediatr (Phila). 2014 Jan;53(1):71-81. doi: 10.1177/0009922813500846
  7. Leung A, Mui Chung Y, Lau James T. Hirschsprungs Disease and Mongolism J Natl Med Assoc. 1986 May; 78(5): 443, 446. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571353/ (In Russ.)
  8. Clarke SA, Van der Avoirt A. Imperforate anus, Hirschsprungs disease, and trisomy 21: a rare combination. J Pediatr Surg. 1999 Dec;34(12):1874. doi: 10.1016/S0022-3468(99)90337-8
  9. Friedmacher F, Puri P. Hirschsprungs disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality. Pediatr Surg Int. 2013 Sep;29(9):937-46. doi: 10.1007/s00383-013-3361-1. doi: 10.1007/s00383-013-3361-1
  10. Alexandrov PN, Percy ME, Lukiw WJ. Chromosome 21-Encoded microRNAs (mRNAs): impact on downs syndrome and Trisomy-21 linked disease. Cell Mol Neurobiol. 2018 Apr;38(3):769-74. doi: 10.1007/s10571-017-0514-0
  11. Soret R, Mennetrey M, Bergeron KF, Dariel A, Neunlist M, Grunder F, Faure C, Silversides DW, Pilon N. A collagen VI-dependent pathogenic mechanism for Hirschsprungs disease. J Clin Invest. 2015 Dec;125(12):4483-96. doi: 10.1172/JCI83178
  12. Quinn FM, Surana R, Puri P. The influence of trisomy 21 on outcome in children with Hirschsprungs disease. J Pediatr Surg. 1994 Jun;29(6):781-83. doi: 10.1016/0022-3468(94)90369-7
  13. Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet. 1990 Mar;46(3):568-80. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1683643/
  14. Besson WT 3rd, Kirby ML, Van Mierop LH, Teabeaut JR 2nd. Effects of the size of lesions of the cardiac neural crest at various embryonic ages on incidence and type of cardiac defects. Circulation. 1986 Feb;73(2):360-64. https://www.semanticscholar.org/paper/Effects-of-the-size-of-lesions-of-the-cardiac-crest-Besson
  15. Kwendakwema N, Al-Dulaimi R, Presson AP, Zobell S, Stevens AM, Bucher BT, Barnhart DC, Rollins MD. Enterocolitis and bowel function in children with Hirschsprung disease and trisomy 21. J Pediatr Surg. 2016 Dec;51(12):2001-2004. doi: 10.1016/j.jpedsurg.2016.09.026
  16. Carneiro PR, Brereton RJ, Drake DP, Kiely EM, Spitz L, Turnock R. Enterocolitis in Hirschsprungs disease. Pediatr Surg Int. 1992;7:356-60. https://link.springer.com/article/10.1007/BF00176592
  17. Teitelbaum DH, Qualman SJ, Caniano DA. Hirschsprungs disease. Identification of risk factors for enterocolitis. Ann Surg. 1988 Mar;207(3):240-44. doi: 10.1097/00000658-198803000-00003
  18. Menezes M, Puri P. Long-term outcome of patients with enterocolitis complicating Hirschsprungs disease. Pediatr Surg Int. 2006 Apr;22(4):316-18. doi: 10.1007/s00383-006-1639-2
  19. Hackam DJ, Reblock K, Barksdale EM, Redlinger R, Lynch J, Gaines BA. The influence of Downs syndrome on the management and outcome of children with Hirschsprungs disease. J Pediatr Surg. 2003 Jun;38(6):946-49. doi: 10.1016/S0022-3468(03)00129-5
  20. Morabito A, Lall A, Gull S, Mohee A, Bianchi A. The impact of Downs syndrome on the immediate and long-term outcomes of children with Hirschsprungs disease. Pediatr Surg Int. 2006 Feb;22(2):179-81. doi: 10.1007/s00383-005-1617-0
  21. Moore SW, Johnson AG. Hirschsprungs disease: genetic and functional associations of Downs and Waardenburg syndromes. Semin Pediatr Surg. 1998 Aug;7(3):156-61. doi: 10.1016/S1055-8586(98)70011-3
  22. Rescorla FJ, Morrison AM, Engles D, West KW, Grosfeld JL. Hirschsprungs disease. Evaluation of mortality and long-term function in 260 cases. Arch Surg. 1992;127(8):934-42. doi: 10.1001/archsurg.1992.01420080068011
  23. Blane CE, Elhalaby E, Coran AG. Enterocolitis following endorectal pull-through procedure in children with Hirschsprungs disease. Pediatr Radiol. 1994;24(3):164-66. doi: 10.1007/BF02012178
  24. Austin KM. The pathogenesis of Hirschsprungs disease-associated enterocolitis. Semin Pediatr Surg. 2012 Nov;21(4):319-27. doi: 10.1053/j.sempedsurg.2012.07.006
  25. Vieten D, Spicer R. Enterocolitis complicating Hirschsprungs disease. Semin Pediatr Surg. 2004 Nov;13(4):263-72. doi: 10.1053/j.sempedsurg.2004.10.014
  26. Rintala RJ, Pakarinen MP. Long-term outcomes of Hirschsprungs disease. Semin Pediatr Surg. 2012 Nov;21(4):336-43. doi: 10.1053/j.sempedsurg.2012.07.008
  27. Moore SW. Down syndrome and the enteric nervous system. Pediatr Surg Int. 2008 Aug;24(8):873-83. doi: 10.1007/s00383-008-2188-7
  28. Gross ER, Gershon MD, Margolis KG, Gertsberg ZV, Li Z, Cowles RA. Neuronal serotonin regulates growth of the intestinal mucosa in mice. Gastroenterology. 2012 Aug;143(2):408-17.e2. doi: 10.1053/j.gastro.2012.05.007
  29. Liu MT, Kuan YH, Wang J, Hen R, Gershon MD. 5-HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice. J Neurosci. 2009 Aug 5;29(31):9683-99. doi: 10.1523/JNEUROSCI.1145-09.2009
  30. Fiorica-Howells E, Maroteaux L, Gershon MD. Serotonin and the 5-HT(2B) receptor in the development of enteric neurons. J Neurosci. 2000 Jan 1;20(1):294-305. doi: 10.1523/JNEUROSCI.20-01-00294.2000
  31. Li Z, Chalazonitis A, Huang YY, Mann JJ, Margolis KG, Yang QM, Kim DO, Coté F, Mallet J, Gershon MD. Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J Neurosci. 2011 Jun 15;31(24):8998-9009. doi: 10.1523/JNEUROSCI.6684-10.2011
  32. Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science. 2003 Jan 3;299(5603):76. doi: 10.1126/science.1078197
  33. Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes. 2013 Feb;20(1):14-21. doi: 10.1097/MED.0b013e32835bc703
  34. Yu H, Zheng BJ, Pan WK, Wang HJ, Xie C, Zhao YY, Chen XL, Liu Y, Gao Y. Combination of exogenous cell transplantation and 5-HT4 receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model. Exp Cell Res. 2017 Feb 1;351(1):36-42. doi: 10.1016/j.yexcr.2016.12.022
  35. Coyle D, Murphy JM, Doyle B, ODonnell AM, Gillick J, Puri P. Altered tryptophan hydroxylase 2 expression in enteric serotonergic nerves in Hirschsprungs-associated enterocolitis. World J Gastroenterol. 2016 May 21;22(19):4662-72. Published online 2016 May 21. doi: 10.3748/wjg.v22.i19.4662
  36. Wilkinson DJ, Bethell GS, Shukla R, Kenny SE, Edgar DH. Isolation of enteric nervous system progenitor cells from the aganglionic gut of patients with Hirschsprungs disease. PLoS One. 2015 May 18;10(5):e0125724. doi: 10.1371/journal.pone.0125724
  37. Nelson KB, Grether JK, Croen LA, Dambrosia JM, Dickens BF, Jelliffe LL, Hansen RL, Phillips TM. Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol. 2001 May;49(5):597-606. doi: 10.1002/ana.1024
  38. Nelson PG, Kuddo T, Song EY, Dambrosia JM, Kohler S, Satyanarayana G, Vandunk C, Grether JK, Nelson KB. Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome. Int J Dev Neurosci. 2006 Feb;24(1):73-80. doi: 10.1016/j.ijdevneu.2005.10.003
  39. Wu JY, Henins KA, Gressens P, Gozes I, Fridkin M, Brenneman DE, Hill JM. Neurobehavioral development of neonatal mice following blockade of VIP during the early embryonic period. Peptides. 1997;18(8):1131-37. doi: 10.1016/S0196-9781(97)00146-0
  40. Hill JM, Ades AM, McCune SK, Sahir N, Moody EM, Abebe DT, Crnic LS, Brenneman DE. Vasoactive intestinal peptide in the brain of a mouse model for Down syndrome. Exp Neurol. 2003 Sep;183(1):56-65. doi: 10.1016/S0014-4886(03)00164-X
  41. Zaitoun I, Erickson CS, Barlow AJ, Klein TR, Heneghan AF, Pierre JF, Epstein ML, Gosain A. Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprungs disease. Neurogastroenterol Motil. 2013 Mar;25(3):e233-44. doi: 10.1111/nmo.12083
  42. Coyle D, ODonnell AM, Gillick J, Puri P. Altered neurotransmitter expression profile in the ganglionic bowel in Hirschsprungs disease. J Pediatr Surg. 2016 May;51(5):762-69. doi: 10.1016/j.jpedsurg.2016.02.018
  43. Langer JC. Persistent obstructive symptoms after surgery for Hirschsprungs disease: development of a diagnostic and therapeutic algorithm. J Pediatr Surg. 2004 Oct;39(10):1458-62. doi: 10.1016/j.jpedsurg.2004.06.008
  44. Wilcox DT, Bruce J, Bowen J, Bianchi A. One-stage neonatal pull-through to treat Hirschsprungs disease. J Pediatr Surg. 1997 Feb;32(2):243-45; discussion 245-47. doi: 10.1016/S0022-3468(97)90187-1
  45. Catto-Smith AG, Trajanovska M, Taylor RG. Long-term continence in patients with Hirschsprungs disease and Down syndrome. J Gastroenterol Hepatol. 2006 Apr;21(4):748-53. doi: 10.1111/j.1440-1746.2005.03996.x
  46. Moore SW, Albertyn R, Cywes S. Clinical outcome and long-term quality of life after surgical correction of Hirschsprungs disease. J Pediatr Surg. 1996 Nov;31(11):1496-502. doi: 10.1016/S0022-3468(96)90164-5
  47. Menezes M, Puri P. Long-term clinical outcome in patients with Hirschsprungs disease and associated Downs syndrome. Pediatr Surg. 2005 May;40(5):810-12. doi: 10.1016/j.jpedsurg.2005.01.048
  48. Travassos D, van Herwaarden-Lindeboom M, van der Zee DC. Hirschsprungs disease in children with Down syndrome: a comparative study. Eur J Pediatr Surg. 2011 Aug;21(4):220-23. doi: 10.1055/s-0031-1271735
  49. Govorukhina . Current diagnosis and treatment of Hirschsprungs disease in children. Novosti Khirurgii. 2017;25(5):510-17. doi: 10.18484/2305-0047.2017.5.510 (In Russ.)
  50. Dronov AF, Smirnov AN, Kholostova VV, Zalikhin DV, Mannanov AG. The Soave procedure in Hirschsprung disease of children. Det Khirurgiia. 2016;20(6):303-309. http://www.medlit.ru/journalsview/childsurg/view/journal/2016/issue-6/ (In Russ.)
Address for correspondence:
119991, Russian Federation,
Moscow, Trubetskaya Str., 8-2,
I.M. Sechenov First Moscow
State Medical University,
Department of Pediatric Surgery
And Urology-Andrology,
Tel. +7-985-265-33-02,
e-mail: evgeniyapimenova@list.ru,
Evgeniya S. Pimenova
Information about the authors:
Morozov Dmitry A., MD, Professor, Head of the Department of Pediatric Surgery and Urology-Andrology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.
https://orcid.org/0000-0002-1940-1395
Pimenova Evgeniya S., PhD, Associate Professor of the Department of Pediatric Surgery and Urology-Andrology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.
https://orcid.org/0000-0001-7206-5987
Marchuk Tatyana D., 4-Year Student of the Pediatric Faculty, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.
https://orcid.org/0000-0002-0608-479X
Contacts | ©Vitebsk State Medical University, 2007