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Megacystis-microcolon-intestinal hypoperistalsis syndrome 5(MMIHS5)

MedGen UID:
1782906
Concept ID:
C5543636
Disease or Syndrome
Synonyms: MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS SYNDROME 5; MMIHS5
 
Gene (location): ACTG2 (2p13.1)
 
Monarch Initiative: MONDO:0030329
OMIM®: 619431

Definition

Megacystis-microcolon-intestinal hypoperistalsis syndrome-5 (MMIHS5) is a form of visceral myopathy characterized by significant inter- and intrafamilial variability, with the most severely affected patients exhibiting prenatal bladder enlargement, intestinal malrotation, neonatal functional gastrointestinal obstruction, and chronic dependence on total parenteral nutrition (TPN) and urinary catheterization (Wangler et al., 2014). For a general phenotypic description and discussion of genetic heterogeneity of MMIHS, see MMIHS1 (249210). [from OMIM]

Additional description

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

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.

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.

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.

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.

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.  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.
Megacystis
MedGen UID:
343318
Concept ID:
C1855311
Finding
Dilatation of the bladder postnatally.
Portal hypertension
MedGen UID:
9375
Concept ID:
C0020541
Disease or Syndrome
Increased pressure in the portal vein.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Microcolon
MedGen UID:
82734
Concept ID:
C0266200
Congenital Abnormality
A colon of abnormally small caliber.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.

Professional guidelines

PubMed

Fontanella F, Groen H, Duin LK, Suresh S, Bilardo CM
Ultrasound Obstet Gynecol 2021 Dec;58(6):875-881. doi: 10.1002/uog.23647. PMID: 33864313Free PMC Article
Muto M, Matsufuji H, Taguchi T, Tomomasa T, Nio M, Tamai H, Tamura M, Sago H, Toki A, Nosaka S, Kuroda T, Yoshida M, Nakajima A, Kobayashi H, Sou H, Masumoto K, Watanabe Y, Kanamori Y, Hamada Y, Yamataka A, Shimojima N, Kubota A, Ushijima K, Haruma K, Fukudo S, Araki Y, Kudo T, Obata S, Sumita W, Watanabe T, Fukahori S, Fujii Y, Yamada Y, Jimbo K, Kawai F, Fukuoka T, Onuma S, Morizane T, Ieiri S, Esumi G, Jimbo T, Yamasaki T
Pediatr Int 2018 May;60(5):400-410. doi: 10.1111/ped.13559. PMID: 29878629
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

Prathapan KM, King DE, Raghu VK, Ackerman K, Presel T, Yaworski JA, Ganoza A, Bond G, Sevilla WMA, Rudolph JA, Alissa F
J Pediatr Gastroenterol Nutr 2021 Apr 1;72(4):e81-e85. doi: 10.1097/MPG.0000000000003008. PMID: 33264186Free PMC Article
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
Muto M, Matsufuji H, Taguchi T, Tomomasa T, Nio M, Tamai H, Tamura M, Sago H, Toki A, Nosaka S, Kuroda T, Yoshida M, Nakajima A, Kobayashi H, Sou H, Masumoto K, Watanabe Y, Kanamori Y, Hamada Y, Yamataka A, Shimojima N, Kubota A, Ushijima K, Haruma K, Fukudo S, Araki Y, Kudo T, Obata S, Sumita W, Watanabe T, Fukahori S, Fujii Y, Yamada Y, Jimbo K, Kawai F, Fukuoka T, Onuma S, Morizane T, Ieiri S, Esumi G, Jimbo T, Yamasaki T
Pediatr Int 2018 May;60(5):400-410. doi: 10.1111/ped.13559. PMID: 29878629
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
Berdon WE, Baker DH, Blanc WA, Gay B, Santulli TV, Donovan C
AJR Am J Roentgenol 1976 May;126(5):957-64. doi: 10.2214/ajr.126.5.957. PMID: 178239

Diagnosis

Prathapan KM, King DE, Raghu VK, Ackerman K, Presel T, Yaworski JA, Ganoza A, Bond G, Sevilla WMA, Rudolph JA, Alissa F
J Pediatr Gastroenterol Nutr 2021 Apr 1;72(4):e81-e85. doi: 10.1097/MPG.0000000000003008. PMID: 33264186Free PMC Article
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
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
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
Kupferman JC, Stewart CL, Schapfel DM, Kaskel FJ, Fine RN
Pediatr Nephrol 1995 Oct;9(5):626-7. doi: 10.1007/BF00860960. PMID: 8580028

Therapy

Nathan JD, Rudolph JA, Kocoshis SA, Alonso MH, Ryckman FC, Tiao GM
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
Kurume Med J 2004;51(2):125-31. doi: 10.2739/kurumemedj.51.125. PMID: 15373229
Doğruyol H, Günay U, Esmer A, Kahveci R
Z Kinderchir 1987 Oct;42(5):321-3. doi: 10.1055/s-2008-1075614. PMID: 3687238

Prognosis

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
Kalsbeek A, Dhar-Dass R, Hanan A, Al-Haddad E, William I, Alazraki A, Poulik J, McCollum K, Almashad A, Shehata BM
Fetal Pediatr Pathol 2022 Oct;41(5):749-758. Epub 2021 Aug 12 doi: 10.1080/15513815.2021.1964656. PMID: 34383618
Prathapan KM, King DE, Raghu VK, Ackerman K, Presel T, Yaworski JA, Ganoza A, Bond G, Sevilla WMA, Rudolph JA, Alissa F
J Pediatr Gastroenterol Nutr 2021 Apr 1;72(4):e81-e85. doi: 10.1097/MPG.0000000000003008. PMID: 33264186Free PMC Article
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
Kupferman JC, Stewart CL, Schapfel DM, Kaskel FJ, Fine RN
Pediatr Nephrol 1995 Oct;9(5):626-7. doi: 10.1007/BF00860960. PMID: 8580028

Clinical prediction guides

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
Fontanella F, Groen H, Duin LK, Suresh S, Bilardo CM
Ultrasound Obstet Gynecol 2021 Dec;58(6):875-881. doi: 10.1002/uog.23647. PMID: 33864313Free PMC Article
Prathapan KM, King DE, Raghu VK, Ackerman K, Presel T, Yaworski JA, Ganoza A, Bond G, Sevilla WMA, Rudolph JA, Alissa F
J Pediatr Gastroenterol Nutr 2021 Apr 1;72(4):e81-e85. doi: 10.1097/MPG.0000000000003008. PMID: 33264186Free PMC Article
Kandler JL, Sklirou E, Woerner A, Walsh L, Cox E, Xue Y
Mol Genet Genomic Med 2020 Nov;8(11):e1516. Epub 2020 Oct 8 doi: 10.1002/mgg3.1516. PMID: 33031641Free 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

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