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Genetic Aspect of Allied Disorders of Hirschsprung’s Disease

  • Kosuke KirinoEmail author
  • Koichiro Yoshimaru
Chapter

Abstract

Allied disorders of Hirschsprung’s disease (ADHD) have been proposed to be the concept of the functional obstruction of the intestine with the presence of ganglion cells in the terminal rectum. Coordinated action of the enteric nervous system (ENS), interstitial cells of Cajal (ICC), and smooth muscle cells (SMCs) is indispensable to normal gastrointestinal motility. Developmental defects affecting specific cell types or disturbing proper functioning of the ENS, ICC, or SMCs may result in variable degrees of abnormal motility, eventually leading to the development of intestinal neuromuscular disorders. In this chapter, we will discuss an overview of genetics of ADHD.

Keywords

Allied disorders of Hirschsprung’s disease Enteric nervous system Enteric neuropathies Interstitial cells of Cajal Smooth muscle cells Enteric myopathies ACTG2 MYH11 LMOD1 MYLK MYL9 

References

  1. 1.
    Muto M, et al. Japanese clinical practice guidelines for allied disorders of Hirschsprung’s disease, 2017. Pediatr Int. 2018;60:400–10.CrossRefPubMedGoogle Scholar
  2. 2.
    Taguchi T, et al. The incidence and outcome of allied disorders of Hirschsprung’s disease in Japan: results from a nationwide survey. Asian J Surg. 2017;40:29–34.CrossRefPubMedGoogle Scholar
  3. 3.
    De GR, Sarnelli G, Corinaldesi R, Stanghellini V. Advances in our understanding of the pathology of chronic intestinal pseudo-obstruction. Gut. 2004;53:1549–52.CrossRefGoogle Scholar
  4. 4.
    Moore SW. Advances in understanding functional variations in the Hirschsprung disease spectrum (variant Hirschsprung disease). Pediatr Surg Int. 2017;33:285–98.CrossRefPubMedGoogle Scholar
  5. 5.
    Rao M, Gershon MD. Neurogastroenterology: the dynamic cycle of life in the enteric nervous system. Nat Rev Gastroenterol Hepatol. 2017;14:453–4.PubMedGoogle Scholar
  6. 6.
    Brosens E, et al. Genetics of enteric neuropathies. Dev Biol. 2016;417:198–208.CrossRefPubMedGoogle Scholar
  7. 7.
    Heanue TA, Pachnis V. Enteric nervous system development and Hirschsprung’s disease: advances in genetic and stem cell studies. Nat Rev Neurosci. 2007;8:466–79.CrossRefPubMedGoogle Scholar
  8. 8.
    Amiel J, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008;45:1–14.CrossRefPubMedGoogle Scholar
  9. 9.
    Obermayr F, Hotta R, Enomoto H, Young HM. Development and developmental disorders of the enteric nervous system. Nat Rev Gastroenterol Hepatol. 2013;10:43–57.CrossRefPubMedGoogle Scholar
  10. 10.
    Bondurand N, Southard-Smith EM. Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: old and new players. Dev Biol. 2016;417:139–57.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Schuchardt A, D’Agati V, Larsson-Blomberg L, Costantini F, Pachnis V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature. 1994;367:380–3.CrossRefPubMedGoogle Scholar
  12. 12.
    Sanchez MP, et al. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature. 1996;382:70–3.CrossRefPubMedGoogle Scholar
  13. 13.
    Pichel JG, et al. Defects in enteric innervation and kidney development in mice lacking GDNF. Nature. 1996;382:73–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Moore MW, et al. Renal and neuronal abnormalities in mice lacking GDNF. Nature. 1996;382:76–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Hosoda K, et al. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell. 1994;79:1267–76.CrossRefPubMedGoogle Scholar
  16. 16.
    Baynash AG, et al. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell. 1994;79:1277–85.CrossRefGoogle Scholar
  17. 17.
    Shen L, et al. Gdnf haploin sufficiency causes Hirschsprung-like intestinal obstruction and early-onset lethality in mice. Am J Hum Genet. 2002;70:435–47.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yamada T, et al. Reduced expression of the endothelin receptor type B gene in piebald mice caused by insertion of a retroposon-like element in intron 1. J Biol Chem. 2006;281:10799–807.CrossRefPubMedGoogle Scholar
  19. 19.
    Bates MD, Dunagan DT, Welch LC, Kaul A, Harvey RP. The Hlx homeobox transcription factor is required early in enteric nervous system development. BMC Dev Biol. 2006;6:33.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Chalazonitis A, et al. Neurotrophin-3 is required for the survival-differentiation of subsets of developing enteric neurons. J Neurosci. 2001;21:5620–36.CrossRefPubMedGoogle Scholar
  21. 21.
    Puig I, et al. Deletion of Pten in the mouse enteric nervous system induces ganglioneuromatosis and mimics intestinal pseudoobstruction. J Clin Invest. 2009;119:3586–96.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hatano M, et al. A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice. J Clin Invest. 1997;100:795–801.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Shirasawa S, et al. Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon. Nat Med. 1997;3:646–50.CrossRefPubMedGoogle Scholar
  24. 24.
    Taguchi T, et al. Isolated intestinal neuronal dysplasia Type B (IND-B) in Japan: results from a nationwide survey. Pediatr Surg Int. 2014;30:815–22.CrossRefPubMedGoogle Scholar
  25. 25.
    Lei J, Howard MJ. Targeted deletion of Hand2 in enteric neural precursor cells affects its functions in neurogenesis, neurotransmitter specification and gangliogenesis, causing functional aganglionosis. Development. 2011;138:4789–800.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Takaki M. Gut pacemaker cells: the interstitial cells of Cajal (ICC). J Smooth Muscle Res. 2003;39:137–61.CrossRefPubMedGoogle Scholar
  27. 27.
    Huizinga JD, Chen JH. Interstitial cells of Cajal: update on basic and clinical science. Curr Gastroenterol Rep. 2014;16:363.CrossRefPubMedGoogle Scholar
  28. 28.
    Streutker CJ, Huizinga JD, Campbell F, Ho J, Riddell RH. Loss of CD117 (c-kit)- and CD34-positive ICC and associated CD34-positive fibroblasts defines a subpopulation of chronic intestinal pseudo-obstruction. Am J Surg Pathol. 2003;27:228–35.CrossRefPubMedGoogle Scholar
  29. 29.
    Jain D, Moussa K, Tandon M, Culpepper-Morgan J, Proctor DD. Role of interstitial cells of Cajal in motility disorders of the bowel. Am J Gastroenterol. 2003;98:618–24.CrossRefPubMedGoogle Scholar
  30. 30.
    Lehtonen HJ, et al. Segregation of a missense variant in enteric smooth muscle actin gamma-2 with autosomal dominant familial visceral myopathy. Gastroenterology. 2012;143:1482–1491.e3.CrossRefPubMedGoogle Scholar
  31. 31.
    Holla OL, Bock G, Busk OL, Isfoss BL. Familial visceral myopathy diagnosed by exome sequencing of a patient with chronic intestinal pseudo-obstruction. Endoscopy. 2014;46:533–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Thorson W, et al. De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis. Hum Genet. 2014;133:737–42.CrossRefPubMedGoogle Scholar
  33. 33.
    Wangler MF, et al. Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome. PLoS Genet. 2014;10:e1004258.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Gauthier J, et al. A homozygous loss-of-function variant in MYH11 in a case with megacystis-microcolon-intestinal hypoperistalsis syndrome. Eur J Hum Genet. 2015;23:1266–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Yetman AT, Starr LJ. Newly described recessive MYH11 disorder with clinical overlap of Multisystemic smooth muscle dysfunction and Megacystis microcolon hypoperistalsis syndromes. Am J Med Genet A. 2018;176:1011–4.CrossRefPubMedGoogle Scholar
  36. 36.
    Halim D, et al. Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice. Proc Natl Acad Sci U S A. 2017;114:E2739–47.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Halim D, et al. Loss-of-function variants in MYLK cause recessive megacystis microcolon intestinal hypoperistalsis syndrome. Am J Hum Genet. 2017;101:123–9.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Moreno CA, et al. Homozygous deletion in MYL9 expands the molecular basis of megacystis-microcolon-intestinal hypoperistalsis syndrome. Eur J Hum Genet. 2018;26:669–75.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Halim D, et al. ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome. Hum Mol Genet. 2016;25:571–83.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Pediatric Surgery, Graduate School of Medical ScienceKyushu UniversityFukuokaJapan

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