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Megacystis-microcolon-intestinal hypoperistalsis syndrome 2(MMIHS2)

MedGen UID:
1788773
Concept ID:
C5543476
Disease or Syndrome
Synonyms: MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS SYNDROME 2; MMIHS2
 
Gene (location): MYH11 (16p13.11)
 
Monarch Initiative: MONDO:0025708
OMIM®: 619351

Definition

Megacystis-microcolon-intestinal hypoperistalsis syndrome-2 (MMIHS2) is characterized by prenatal bladder enlargement, neonatal functional gastrointestinal obstruction, and chronic dependence on total parenteral nutrition and urinary catheterization. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure (summary by Wang et al., 2019). For a discussion of genetic heterogeneity of MMIHS, see 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
Anuria
MedGen UID:
358
Concept ID:
C0003460
Disease or Syndrome
Absence of urine, clinically classified as below 50ml/day.
Megacystis
MedGen UID:
343318
Concept ID:
C1855311
Finding
Dilatation of the bladder postnatally.
Fetal megacystis
MedGen UID:
419338
Concept ID:
C2931117
Disease or Syndrome
Fetal megacystis is an abnormally enlarged bladder identified at any gestational age.
Renal cortical hyperechogenicity
MedGen UID:
1770764
Concept ID:
C5421632
Finding
Increased echogenecity of the kidney cortex.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Thoracic aortic aneurysm
MedGen UID:
56525
Concept ID:
C0162872
Anatomical Abnormality
An abnormal localized widening (dilatation) of the thoracic aorta.
Bidirectional shunt
MedGen UID:
507286
Concept ID:
C0428872
Acquired Abnormality
Pattern of blood flow in the heart that deviates from the normal circuit of the circulatory system from both right side of the heart to the left and vice versa.
Elevated pulmonary artery pressure
MedGen UID:
812247
Concept ID:
C3805917
Finding
An abnormally elevated blood pressure in the circulation of the pulmonary artery.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Prune belly syndrome
MedGen UID:
18718
Concept ID:
C0033770
Disease or Syndrome
In its rare complete form, 'prune belly' syndrome (PBS) comprises megacystis (massively enlarged bladder) with disorganized detrusor muscle, cryptorchidism, and thin abdominal musculature with overlying lax skin (summary by Weber et al., 2011).
Ileal atresia
MedGen UID:
451021
Concept ID:
C0266176
Congenital Abnormality
An abnormal closure, or atresia of the tubular structure of the ileum.
Microcolon
MedGen UID:
82734
Concept ID:
C0266200
Congenital Abnormality
A colon of abnormally small caliber.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Bronchomalacia
MedGen UID:
82679
Concept ID:
C0264353
Disease or Syndrome
Weakness or softness of the cartilage in the walls of the bronchial tubes.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Respiratory failure requiring assisted ventilation
MedGen UID:
870821
Concept ID:
C4025279
Finding
A state of respiratory distress that requires a life saving intervention in the form of gaining airway access and instituting positive pressure ventilation.
Peritonitis
MedGen UID:
14697
Concept ID:
C0031154
Pathologic Function
Inflammation of the peritoneum.
Pyelonephritis
MedGen UID:
19590
Concept ID:
C0034186
Disease or Syndrome
An inflammation of the kidney involving the parenchyma of kidney, the renal pelvis and the kidney calices.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Mydriasis
MedGen UID:
10145
Concept ID:
C0026961
Sign or Symptom
Abnormal dilatation of the iris.

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
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

Recent clinical studies

Etiology

Billon C, Piccoli GB, de Sainte Agathe JM, Stoeva R, Derive N, Heidet L, Berrebi D, Bruneval P, Jeunemaitre X, Hureaux M
Mol Genet Genomics 2024 Apr 16;299(1):44. doi: 10.1007/s00438-024-02136-3. PMID: 38625590
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
Raofi V, Beatty E, Testa G, Abcarian H, Oberholzer J, Sankary H, Grevious M, Benedetti E
J Pediatr Surg 2008 Feb;43(2):e9-e11. doi: 10.1016/j.jpedsurg.2007.09.073. PMID: 18280270
Shono T, Suita S, Taguchi T, Nagasaki A
Eur J Pediatr Surg 1992 Feb;2(1):52-5. doi: 10.1055/s-2008-1063402. PMID: 1571330

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
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
Tuzovic L, Anyane-Yeboa K, Mills A, Glassberg K, Miller R
Fetal Diagn Ther 2014;36(1):74-80. Epub 2014 Feb 21 doi: 10.1159/000357703. PMID: 24577413
Annerén G, Meurling S, Olsen L
Am J Med Genet 1991 Nov 1;41(2):251-4. doi: 10.1002/ajmg.1320410224. PMID: 1785644
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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
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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
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JPEN J Parenter Enteral Nutr 1986 Mar-Apr;10(2):242-4. doi: 10.1177/0148607186010002242. PMID: 3083140

Prognosis

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
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
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
De Sousa J, Upadhyay V, Stone P
Fetal Diagn Ther 2016;39(2):152-7. Epub 2015 Dec 9 doi: 10.1159/000442050. PMID: 26645214
Masetti M, Rodriguez MM, Thompson JF, Pinna AD, Kato T, Romaguera RL, Nery JR, DeFaria W, Khan MF, Verzaro R, Ruiz P, Tzakis AG
Transplantation 1999 Jul 27;68(2):228-32. doi: 10.1097/00007890-199907270-00011. PMID: 10440392

Clinical prediction guides

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
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
Richardson CE, Morgan JM, Jasani B, Green JT, Rhodes J, Williams GT, Lindstrom J, Wonnacott S, Thomas GA, Smith V
Gastroenterology 2001 Aug;121(2):350-7. doi: 10.1053/gast.2001.26320. PMID: 11487544

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

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