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Megacystis-microcolon-intestinal hypoperistalsis syndrome 3(MMIHS3)

MedGen UID:
1780019
Concept ID:
C5543513
Disease or Syndrome
Synonyms: MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS SYNDROME 3; MMIHS3
 
Gene (location): LMOD1 (1q32.1)
 
Monarch Initiative: MONDO:0030294
OMIM®: 619362

Definition

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital defect of visceral smooth muscle, primarily affecting females who present at birth with functional obstruction of the intestine, microcolon, dilation of the bladder, and secondary hydronephrosis. Total parenteral nutrition, adequate intermittent catheterization of bladder, and surgical corrections for intestinal malrotation are frequent modes of treatment for this disease without which rapid death ensues. In some instances, multivisceral organ transplantation has been undertaken with some success. Despite these clinical interventions, MMIHS often leads to premature death due to complications of therapy (summary by Halim et al., 2017). For a discussion of genetic heterogeneity of MMIHS, see 249210. [from OMIM]

Additional description

From MedlinePlus Genetics
Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a severe disorder affecting the muscles that line the bladder and intestines. It is characterized by impairment of the muscle contractions that move food through the digestive tract (peristalsis) and empty the bladder.

Some of the major features of MMIHS can be recognized before birth using ultrasound imaging. Affected fetuses have an enlarged bladder (megacystis) because it does not empty. In addition, the large intestine (colon) is abnormally narrow (microcolon) because of a shortage of functional muscle lining it. Intestinal and bladder problems persist throughout life.

After birth, the continued impairment of peristalsis (hypoperistalsis) often causes a digestive condition called intestinal pseudo-obstruction. This condition, which mimics a physical blockage (obstruction) of the intestines but without an actual blockage, leads to a buildup of partially digested food in the intestines. This buildup can cause abdominal swelling (distention) and pain, nausea, and vomiting. The vomit usually contains a green or yellow digestive fluid called bile. Because digestion is impeded and the body does not get the nutrients from food, nutritional support is usually needed, which is given through intravenous feedings (parenteral nutrition). While some affected individuals rely solely on intravenous feedings, others require it only on occasion. Long-term use of parenteral nutrition can lead to liver problems.

The life expectancy of people with MMIHS is shorter than normal, often due to malnutrition, overwhelming infection (sepsis), or the failure of multiple organs.

The reduced ability to pass urine also contributes to painful distention of the abdomen. Many people with MMIHS require placement of a tube (urinary catheter) to remove urine from the bladder.

Another abnormality in some people with MMIHS is intestinal malrotation, in which the intestines do not fold properly. Instead, they twist abnormally, often causing a blockage. Individuals with MMIHS can also develop problems with the kidneys or the ureters, which are the ducts that carry urine from the kidneys to the bladder.  https://medlineplus.gov/genetics/condition/megacystis-microcolon-intestinal-hypoperistalsis-syndrome

Clinical features

From HPO
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Hydroureter
MedGen UID:
101073
Concept ID:
C0521620
Anatomical Abnormality
The distention of the ureter with urine.
Fetal megacystis
MedGen UID:
419338
Concept ID:
C2931117
Disease or Syndrome
Fetal megacystis is an abnormally enlarged bladder identified at any gestational age.
Abnormal heart morphology
MedGen UID:
6748
Concept ID:
C0018798
Congenital Abnormality
Any structural anomaly of the heart.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Microcolon
MedGen UID:
82734
Concept ID:
C0266200
Congenital Abnormality
A colon of abnormally small caliber.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.

Professional guidelines

PubMed

Lombardi L, Bruder E, Pio L, Nozza P, Thai E, Lerone M, Del Rossi C, Mattioli G, Silini EM, Paraboschi I, Martucciello G
J Pediatr Gastroenterol Nutr 2018 Mar;66(3):383-386. doi: 10.1097/MPG.0000000000001727. PMID: 28837505
Osborne NG, Bonilla-Musoles F, Machado LE, Raga F, Bonilla F Jr, Ruiz F, Pérez Guardia CM, Ahluwalia B
J Ultrasound Med 2011 Jun;30(6):833-41. doi: 10.7863/jum.2011.30.6.833. PMID: 21632999
Muller F, Dreux S, Vaast P, Dumez Y, Nisand I, Ville Y, Boulot P, Guibourdenche J, Althusser M, Blin G, Gautier E, Lespinard C, Perrotin F, Poulain P, Sarramon MF; Study Group of the French Fetal Medicine Society
Prenat Diagn 2005 Mar;25(3):203-9. doi: 10.1002/pd.1088. PMID: 15791664

Recent clinical studies

Etiology

Pellegrino C, Barone G, Capitanucci ML, Zaccara AM, Fusaro F, Iacobelli BD, Scorletti F, Conforti A, De Angelis P, Diamanti A, Caldaro T, Tambucci R, Sollini ML, Forlini V, Mosiello G
Pediatr Surg Int 2024 May 7;40(1):124. doi: 10.1007/s00383-024-05711-2. PMID: 38713441
Fontanella F, Maggio L, Verheij JBGM, Duin LK, Adama Van Scheltema PN, Cohen-Overbeek TE, Pajkrt E, Bekker M, Willekes C, Bax CJ, Gracchi V, Oepkes D, Bilardo CM
Ultrasound Obstet Gynecol 2019 Jun;53(6):779-787. doi: 10.1002/uog.19182. PMID: 30043466Free PMC Article
Hugar LA, Chaudhry R, Fuller TW, Cannon GM, Schneck FX, Ost MC, Stephany HA
Urology 2018 Sep;119:127-132. Epub 2018 May 9 doi: 10.1016/j.urology.2018.05.002. PMID: 29752972
Taghavi K, Sharpe C, Stringer MD
J Pediatr Urol 2017 Feb;13(1):7-15. Epub 2016 Oct 8 doi: 10.1016/j.jpurol.2016.09.003. PMID: 27889224
Muller F, Dreux S, Vaast P, Dumez Y, Nisand I, Ville Y, Boulot P, Guibourdenche J, Althusser M, Blin G, Gautier E, Lespinard C, Perrotin F, Poulain P, Sarramon MF; Study Group of the French Fetal Medicine Society
Prenat Diagn 2005 Mar;25(3):203-9. doi: 10.1002/pd.1088. PMID: 15791664

Diagnosis

Pellegrino C, Barone G, Capitanucci ML, Zaccara AM, Fusaro F, Iacobelli BD, Scorletti F, Conforti A, De Angelis P, Diamanti A, Caldaro T, Tambucci R, Sollini ML, Forlini V, Mosiello G
Pediatr Surg Int 2024 May 7;40(1):124. doi: 10.1007/s00383-024-05711-2. PMID: 38713441
Devavarapu PKV, Uppaluri KR, Nikhade VA, Palasamudram K, Sri Manjari K
Clin J Gastroenterol 2024 Jun;17(3):383-395. Epub 2024 Mar 9 doi: 10.1007/s12328-024-01934-x. PMID: 38461165
Lu W, Xiao Y, Huang J, Tao Y, Yan W, Lu L, Cao Y, Cai W
J Pediatr Gastroenterol Nutr 2016 Dec;63(6):624-626. doi: 10.1097/MPG.0000000000001204. PMID: 27007401
Soh H, Fukuzawa M, Kubota A, Kawahara H, Ueno T, Taguchi T
J Pediatr Surg 2015 Dec;50(12):2048-50. Epub 2015 Aug 28 doi: 10.1016/j.jpedsurg.2015.08.026. PMID: 26413901
Annerén G, Meurling S, Olsen L
Am J Med Genet 1991 Nov 1;41(2):251-4. doi: 10.1002/ajmg.1320410224. PMID: 1785644

Therapy

Okada M, Sato M, Ogura M, Kamei K, Matsuoka K, Ito S
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J Pediatr Surg 2007 Jan;42(1):143-7. doi: 10.1016/j.jpedsurg.2006.09.049. PMID: 17208555
Hikida S, Tanaka Y, Tsuru T, Ohtani M, Kobayashi H, Asagiri K, Akiyoshi K, Nakamizo H, Fukahori S, Soejima H, Shirouzu Y, Tanigawa H, Shirouzu K, Mizote H
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Annerén G, Meurling S, Olsen L
Am J Med Genet 1991 Nov 1;41(2):251-4. doi: 10.1002/ajmg.1320410224. PMID: 1785644
Doğruyol H
Turk J Pediatr 1989 Jul-Sep;31(3):253-6. PMID: 2485993

Prognosis

Devavarapu PKV, Uppaluri KR, Nikhade VA, Palasamudram K, Sri Manjari K
Clin J Gastroenterol 2024 Jun;17(3):383-395. Epub 2024 Mar 9 doi: 10.1007/s12328-024-01934-x. PMID: 38461165
Nakamura H, O'Donnell AM, Puri P
Pediatr Surg Int 2019 Feb;35(2):175-180. Epub 2018 Nov 1 doi: 10.1007/s00383-018-4390-6. PMID: 30386895
Taghavi K, Sharpe C, Stringer MD
J Pediatr Urol 2017 Feb;13(1):7-15. Epub 2016 Oct 8 doi: 10.1016/j.jpurol.2016.09.003. PMID: 27889224
Halim D, Hofstra RM, Signorile L, Verdijk RM, van der Werf CS, Sribudiani Y, Brouwer RW, van IJcken WF, Dahl N, Verheij JB, Baumann C, Kerner J, van Bever Y, Galjart N, Wijnen RM, Tibboel D, Burns AJ, Muller F, Brooks AS, Alves MM
Hum Mol Genet 2016 Feb 1;25(3):571-83. Epub 2015 Dec 8 doi: 10.1093/hmg/ddv497. PMID: 26647307
Soh H, Fukuzawa M, Kubota A, Kawahara H, Ueno T, Taguchi T
J Pediatr Surg 2015 Dec;50(12):2048-50. Epub 2015 Aug 28 doi: 10.1016/j.jpedsurg.2015.08.026. PMID: 26413901

Clinical prediction guides

Billon C, Molin A, Poirsier C, Clemenson A, Dauge C, Grelet M, Sigaudy S, Patrier S, Goldenberg A, Layet V, Tantau J, Fleury C, Liard A, Diguet A, Fritih R, Verspyck E, Rendu J, Boutaud L, Tessier A, Thomas S, Razavi F, Achaiaa A, Elkhartoufi N, Hakkakian L, Magnin E, Bôle-Feysot C, Masson C, Ville Y, Roth P, Prieur F, Bessieres B, Bonniere M, Attie-Bitach T
Clin Genet 2020 Sep;98(3):261-273. Epub 2020 Aug 4 doi: 10.1111/cge.13801. PMID: 32621347
Halim D, Hofstra RM, Signorile L, Verdijk RM, van der Werf CS, Sribudiani Y, Brouwer RW, van IJcken WF, Dahl N, Verheij JB, Baumann C, Kerner J, van Bever Y, Galjart N, Wijnen RM, Tibboel D, Burns AJ, Muller F, Brooks AS, Alves MM
Hum Mol Genet 2016 Feb 1;25(3):571-83. Epub 2015 Dec 8 doi: 10.1093/hmg/ddv497. PMID: 26647307
Gauthier J, Ouled Amar Bencheikh B, Hamdan FF, Harrison SM, Baker LA, Couture F, Thiffault I, Ouazzani R, Samuels ME, Mitchell GA, Rouleau GA, Michaud JL, Soucy JF
Eur J Hum Genet 2015 Sep;23(9):1266-8. Epub 2014 Nov 19 doi: 10.1038/ejhg.2014.256. PMID: 25407000Free PMC Article
Wangler MF, Gonzaga-Jauregui C, Gambin T, Penney S, Moss T, Chopra A, Probst FJ, Xia F, Yang Y, Werlin S, Eglite I, Kornejeva L, Bacino CA, Baldridge D, Neul J, Lehman EL, Larson A, Beuten J, Muzny DM, Jhangiani S; Baylor-Hopkins Center for Mendelian Genomics, Gibbs RA, Lupski JR, Beaudet A
PLoS Genet 2014 Mar;10(3):e1004258. Epub 2014 Mar 27 doi: 10.1371/journal.pgen.1004258. PMID: 24676022Free PMC Article
Muller F, Dreux S, Vaast P, Dumez Y, Nisand I, Ville Y, Boulot P, Guibourdenche J, Althusser M, Blin G, Gautier E, Lespinard C, Perrotin F, Poulain P, Sarramon MF; Study Group of the French Fetal Medicine Society
Prenat Diagn 2005 Mar;25(3):203-9. doi: 10.1002/pd.1088. PMID: 15791664

Recent systematic reviews

Sandy NS, Huysentruyt K, Mulder DJ, Warner N, Chong K, Morel C, AlQahtani S, Wales PW, Martin MG, Muise AM, Avitzur Y
J Pediatr Gastroenterol Nutr 2022 May 1;74(5):575-581. doi: 10.1097/MPG.0000000000003400. PMID: 35149643Free PMC Article
Nakamura H, O'Donnell AM, Puri P
Pediatr Surg Int 2019 Feb;35(2):175-180. Epub 2018 Nov 1 doi: 10.1007/s00383-018-4390-6. PMID: 30386895
Taghavi K, Sharpe C, Stringer MD
J Pediatr Urol 2017 Feb;13(1):7-15. Epub 2016 Oct 8 doi: 10.1016/j.jpurol.2016.09.003. PMID: 27889224

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