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Familial megacystis microcolon intestinal hypoperistalsis syndrome: a systematic review

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Abstract

Background

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare and severe disorder of functional obstruction affecting bladder and bowel, usually diagnosed in the neonatal period. Over 230 cases have been reported since Berdon and colleagues first described this clinical entity in 1976. The exact pathogenesis of MMIHS is unknown. Familial occurrence of MMIHS has been reported and could offer insight into the aetiology of this disease. The purpose of this study was to systematically review the published literature for the evidence of familial MMIHS and to characterise these presentations.

Methods

A literature search was performed using the keywords “megacystis microcolon intestinal hypoperistalsis” (1976–2013). Retrieved articles, including additional studies from reference lists, were reviewed for consanguinity between parents and recurrence of MMIHS between siblings. Data were extracted for cases where familial MMIHS was present.

Results

A total of 47 patients were reported in which familial MMIHS was likely or confirmed. 15 sibling sets were definitively diagnosed with MMIHS (14 pairs and one set of three siblings). Four further index patients with a confirmed diagnosis and also one of the sibling pairs were reported to have a sibling in which MMIHS was probable. Consanguinity between parents was present in four of the confirmed sibling sets and in an additional seven individual cases. The outcome for familial MMIHS is generally poor. Multiple sibling fatalities were frequent and in only one family were both siblings’ survivors at the time of reporting.

Conclusion

Consanguinity between parents and recurrence in siblings indicate that MMIHS is inherited in an autosomal recessive manner. With the advent of next generation sequencing, these familial clusters may be key to determining the genetic basis for MMIHS.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Andres AM, Miguel M, De la Torre C, Barrena S, Ramirez M, Hernandez F, Martinez L, Leal N, Ramos E, Prieto G, Lopez Santamaria M, Tovar JA (2010) Chronic idiopathic intestinal pseudo obstruction and Berdon syndrome: still a diagnostic and therapeutic challenge for the pediatric surgeon. Cir Pediatr 23(4):215–221

    PubMed  CAS  Google Scholar 

  3. Kohler 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

    Article  PubMed  CAS  Google Scholar 

  4. Raofi V, Beatty E, Testa G, Abcarian H, Oberholzer J, Sankary H, Grevious M, Benedetti E (2008) Combined living-related segmental liver and bowel transplantation for megacystis-microcolon-intestinal hypoperistalsis syndrome. J Pediatr Surg 43(2):e9–e11

    Article  PubMed  Google Scholar 

  5. Berdon WE, Baker DH, Blanc WA, Gay B, Santulli TV, Donovan C (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

    Article  PubMed  CAS  Google Scholar 

  6. Winter RM, Knowles SA (1986) Megacystis-microcolon-intestinal hypoperistalsis syndrome: confirmation of autosomal recessive inheritance. J Med Genet 23(4):360–362

    Article  PubMed  CAS  Google Scholar 

  7. Patel R, Carty H (1980) Megacystis-microcolon-intestinal hypoperistalsis syndrome: a rare cause of intestinal obstruction in the newborn. Br J Radiol 53(627):249–252

    Article  PubMed  CAS  Google Scholar 

  8. Oliveira G, Boechat MI, Ferreira MA (1983) Megacystis-microcolon-intestinal hypoperistalsis syndrome in a newborn girl whose brother had prune belly syndrome: common pathogenesis? Pediatr Radiol 13(5):294–296

    Article  PubMed  CAS  Google Scholar 

  9. Farrell SA (1988) Intrauterine death in megacystis-microcolon-intestinal hypoperistalsis syndrome. J Med Genet 25(5):350–351

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Garber A, Shohat M, Sarti D (1990) Megacystis-microcolon-intestinal hypoperistalsis syndrome in two male siblings. Prenat Diagn 10(6):377–387

    Article  PubMed  CAS  Google Scholar 

  13. Anneren G, Meurling S, Olsen L (1991) Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), an autosomal recessive disorder: clinical reports and review of the literature. Am J Med Genet 41(2):251–254

    Article  PubMed  CAS  Google Scholar 

  14. Stamm E, King G, Thickman D (1991) Megacystis-microcolon-intestinal hypoperistalsis syndrome: prenatal identification in siblings and review of the literature. J Ultrasound Med 10(10):599–602

    PubMed  CAS  Google Scholar 

  15. Hsu CD, Craig C, Pavlik J, Ninios A (2003) Prenatal diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome in one fetus of a twin pregnancy. Am J Perinatol 20(4):215–218

    Article  PubMed  Google Scholar 

  16. Lopez-Munoz E, Hernandez-Zarco A, Polanco-Ortiz A, Villa-Morales J, Mateos-Sanchez L (2013) Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS): report of a case with prolonged survival and literature review. J Pediatr Urol 9(1):e12–e18

    Article  PubMed  Google Scholar 

  17. Lozoya Araque T, Vila-Vives JM, Perales-Puchalt A, Soler Ferrero I, Quiroga R, Llorens-Salvador R, Abad Carrascosa A, Perales A (2013) Berdon syndrome: intrauterine diagnosis and postnatal outcome. Diagnostico Prenatal 24(1):23–28

    Article  Google Scholar 

  18. Gakmak O, Pektas O, Maden HA (1989) Megacystis-microcolon-intestinal hypoperistalsis syndrome in three siblings. Poster presentation at the Sixth International Congress of Paediatric Surgery, Istanbul

    Google Scholar 

  19. Bloom TLK, Kolon TF (2002) Severe megacystis and bilateral hydronephrosis in a female fetus. Urology 60(4):697

    Article  PubMed  Google Scholar 

  20. Goldberg M, Pruchniewski D, Beale PG, Da Fonseca JMB, Davies MRQ (1996) Megacystis-microcolon-intestinal hypoperistalsis syndrome. Pediatr Surg Int 11(4):246–247

    Article  Google Scholar 

  21. Guze CD, Hyman PE, Payne VJ (1999) Family studies of infantile visceral myopathy: a congenital myopathic pseudo-obstruction syndrome. Am J Med Genet 82(2):114–122

    Article  PubMed  CAS  Google Scholar 

  22. Boissier K, Varlet MN, Chauleur C, Cochin S, Clemenson A, Varlet F, Bellicard E, Chantegret C, Patural H, Seffert P, Chene G (2009) Early fetal megacystis at first trimester: a six-year retrospective study. Gynecol Obstet Fertil 37(2):115–124

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. 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

    Article  PubMed  CAS  Google Scholar 

  25. Junior SR, Moreira MA, Modelli ME, Pereira CR (1996) Megacystis-microcolon-intestinal hypoperistalsis syndrome. A case report. J Pediatr (Rio J) 72(2):109–112

    Article  CAS  Google Scholar 

  26. Al Harbi A, Tawil K, Crankson SJ (1999) Megacystis-microcolon-intestinal hypoperistalsis syndrome associated with megaesophagus. Pediatr Surg Int 15(3–4):272–274

    Article  PubMed  CAS  Google Scholar 

  27. White SM, Chamberlain P, Hitchcock R, Sullivan PB, Boyd PA (2000) Megacystis-microcolon-intestinal hypoperistalsis syndrome: the difficulties with antenatal diagnosis. Case report and review of the literature. Prenat Diagn 20(9):697–700

    Article  PubMed  CAS  Google Scholar 

  28. Narayanan M, Murphy MS, Ainsworth JR, Arul GS (2007) Mydriasis in association with MMIHS in a female infant: evidence for involvement of the neuronal nicotinic acetylcholine receptor. J Pediatr Surg 42(7):1288–1290

    Article  PubMed  CAS  Google Scholar 

  29. Melek M, Edirne Y, Beger B, Cetin M (2009) Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report. Gastroenterol Res Pract 2009:282753

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  32. Ballisty MM, Braithwaite KA, Shehata BM, Dickson PN (2013) Imaging findings in megacystis-microcolon-intestinal hypoperistalsis syndrome. Pediatr Radiol 43(4):454–459

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  34. Stoltenberg C, Magnus P, Skrondal A, Lie RT (1999) Consanguinity and recurrence risk of birth defects: a population-based study. Am J Med Genet 82(5):423–428

    Article  PubMed  CAS  Google Scholar 

  35. Stoll C, Alembik Y, Dott B, Feingold J (1994) Parental consanguinity as a cause of increased incidence of birth defects in a study of 131,760 consecutive births. Am J Med Genet 49(1):114–117

    Article  PubMed  CAS  Google Scholar 

  36. Bittles AH (1994) The role and significance of consanguinity as a demographic variable. Popul Dev Rev 20(3):561–584

    Article  Google Scholar 

  37. McKusick V (2001) Megacystis-microcolon-intestinal hypoperistalsis syndrome. Online mendelian inheritance in man, OMIM. McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and NCBI, National Library of Medicine (Bethesda, MD). http://www.ncbi.nlm.nih.gov/omim/249210#Inheritance-249210

  38. McKusick VA (1998) Mendelian inheritance in man, A catalog of human genes and genetic disorders, 12th edn. Johns Hopkins University Press, Baltimore

    Google Scholar 

  39. Mousa H, Hyman PE, Cocjin J, Flores AF, Di Lorenzo C (2002) Long-term outcome of congenital intestinal pseudo obstruction. Dig Dis Sci 47(10):2298–2305

    Article  PubMed  Google Scholar 

  40. Higman D, Peters P, Stewart M (1992) Familial hollow visceral myopathy with varying urological manifestations. Br J Urol 70(4):435–438

    Article  PubMed  CAS  Google Scholar 

  41. Faure C, Goulet O, Ategbo S, Breton A, Tounian P, Ginies JL, Roquelaure B, Despres C, Scaillon M, Maurage C, Paquot I, Hermier M, De Napoli S, Dabadie A, Huet F, Baudon JJ, Larchet M (1999) Chronic intestinal pseudo obstruction syndrome: clinical analysis, outcome, and prognosis in 105 children. Dig Dis Sci 44(5):953–959

    Article  PubMed  CAS  Google Scholar 

  42. Heneyke S, Smith VV, Spitz L, Milla PJ (1999) Chronic intestinal pseudo-obstruction: treatment and long term follow up of 44 patients. Arch Dis Child 81(1):21–27

    Article  PubMed  CAS  Google Scholar 

  43. Masetti M, Rodriguez MM, Thompson JF, Pinna AD, Kato T, Romaguera RL, Nery JR, DeFaria W, Khan MF, Verzaro R, Ruiz P, Tzakis AG (1999) Multivisceral transplantation for megacystis microcolon intestinal hypoperistalsis syndrome. Transplant 68(2):228–232

    Article  CAS  Google Scholar 

  44. Harper P (2010) Practical genetic counselling, 7th edn. Arnold, London

    Google Scholar 

  45. De Biasi M (2002) Nicotinic mechanisms in the autonomic control of organ systems. J Neurobiol 53(4):568–579

    Article  PubMed  Google Scholar 

  46. Xu W, Orr-Urtreger A, Nigro F, Gelber S, Sutcliffe CB, Armstrong D, Patrick JW, Role LW, Beaudet AL, De Biasi M (1999) Multiorgan autonomic dysfunction in mice lacking the β2 and the β4 subunits of neuronal nicotinic acetylcholine receptors. J Neurosci 19(21):9298–9305

    PubMed  CAS  Google Scholar 

  47. Richardson CE, Morgan JM, Jasani B, Green JT, Rhodes J, Williams GT, Lindstrom J, Wonnacott S, Thomas GA, Smith V (2001) Megacystis-microcolon-intestinal hypoperistalsis syndrome and the absence of the alpha3 nicotinic acetylcholine receptor subunit. Gastroenterol 121(2):350–357

    Article  CAS  Google Scholar 

  48. Lev-Lehman E, Bercovich D, Xu W, Stockton DW, Beaudet 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 

  49. Szigeti R, Chumpitazi BP, Finegold MJ, Ranganathan S, Craigen WJ, Carter BA, Tatevian N (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

    Article  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

    Danielle Mc Laughlin & Prem Puri

  2. Children’s University Hospital, Temple Street, Dublin, Ireland

    Danielle Mc Laughlin

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  1. Danielle Mc Laughlin
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  2. Prem Puri
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Correspondence to Prem Puri.

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Mc Laughlin, D., Puri, P. Familial megacystis microcolon intestinal hypoperistalsis syndrome: a systematic review. Pediatr Surg Int 29, 947–951 (2013). https://doi.org/10.1007/s00383-013-3357-x

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