Women's Health Alliance -Department of Ultrasound.

300 20^th Avenue, Suite 401 - Nashville, TN

Reviewer: Michael Divon, MD

Synonyms: Neonatal hollow visceral myopathy. Berdon syndrome.

Definition: Megacystis-microcolon-intestinal hypoperistalsis syndrome consists of the association of a distended unobstructed bladder, dilated small bowel, microcolon, and decreased or absent peristalsis with ganglion cells present.

Case report: A 38-year-old G₂P₁ woman presented to our diagnostic center for a routine ultrasound examination at 21 weeks. The ultrasonographic examination (fig. 1) revealed a single female fetus with a markedly distended bladder and normal to increased amniotic fluid volume. Other than minimal distension of the renal pelvis, no other abnormalities were detected.

Figure 1: Several views that demonstrate the enlarged bladder (the abdominal portion of the umbilical arteries surround it), reaching up to the chest (second image).

(There is a videoclip available)

The most likely diagnosis consistent with this combination of findings was megacystis-microcolon-hypoperistalsis syndrome. The patient was referred for genetic counseling and the exam was repeated in two weeks to assess the progression of the syndrome. The second exam performed at 23 weeks again demonstrated increased amniotic fluid. The bladder was further distended and extended into the left upper quadrant of the fetus filling the pelvis and part of the abdomen. Due to the poor prognosis, the patient elected to terminate the pregnancy. The autopsy revealed a 560gram female fetus with no external developmental abnormalities (fig. 2-3).

Figure 2: The overall appearance of the fetus is normal.

Figure 3: There is, however, a slight abdominal bulge due to the bladder.

The internal examination revealed a markedly distended bladder filling the abdominal cavity with no urethral stricture or gross evidence of mechanical outlet obstruction (fig. 4-5). Mild hydronephrosis was noted bilaterally without hydroureter.

Figure 4: The bladder in situ and exteriorized. Notice on the first image how the bladder reaches up in the right upper quadrant.

Figure 5: The kidney and bladder preparation. Note the absence of hydroureters in spite of the large bladder.

The uterus and ovaries were unremarkable. The small bowel was shortened length (primarily jejunum and ileum) with mildly decreased caliber of distal ileum without proximal dilatation (fig. 6). The large bowel was normal.

Figure 6: Short and thin small bowel.

These findings confirmed the diagnosis of megacystis-microcolon hyopoperistalsis syndrome.

History: Megacystis-microcolon hyopoperistalsis syndrome is rare and lethal in most cases. It was first described in 1974 by Berdon in 5 female infants, 2 of whom were sisters¹. The first reported ultrasound diagnosis was made by Vezina et al. in 1979[2]. Collectively, there have been at least 45 reported cases [3]^{,[4],[5],[6],,[8],,[10],[11],,[13]}. In all cases, the enlarged bladder and absence of oligohydramnios  typical of this syndrome were easy to define by ultrasound. Polyhydramnios is present in approximately 25% of the cases. The length of gestation and birth weight are within normal limits. There is no universally agreed upon explanation as yet for the etiology and pathogenesis. The diagnosis is simple, the treatment symptomatic, and the outcome fatal.

Etymology: Greek: megaV (megas) = great, strong; kustis (kystis) = bladder, mikros (mikros) = small, little, kwlon (kolon) = colon; upo (hypo) =  under, peri (peri) = around and stalsiV (stalsis) = to contract and Latin: intestinum = the guts (from intus = within).

Prevalence: M1:F4. Megacystis-microcolon-intestinal hypoperistalsis syndrome is more common in females, perhaps due to underdiagnosis in males who are labeled instead as "prune bellyâ€.

Etiology: Most cases are sporadic. An autosomal recessive inheritance has been supported by reports of affected siblings[16][17]^,[18],,[20].

Pathogenesis: A transient anatomical and/or functional urinary tract obstruction has been considered. Srikanth[21] suggested that an intramural inflammatory process affecting the gastrointestinal and urinary tracts could lead to extensive fibrosis. The fibrosis would destroy the intestinal neural network, producing hypoperistalsis and causes neuromuscular incoordination of the bladder. The resulting bladder distension could interfere with the rotation of the intestine causing malrotation. Another theory suggests the urinary tract obstruction in this condition is secondary to the intestinal defect. It is not clear whether this is a primary neuropathy or myopathy14. At pathology, vacuolar degeneration of smooth muscle is observed. The ganglion cell distribution is normal[22]^,[23] but axonal dystrophy of the central, peripheral, and autonomic nervous systems[24] and dysplastic changes associated with increased laminin and fibronectin have been observed suggesting a primary myocellular defect of contractile fiber synthesis. This suggests a defect of glycogen-energy utilization but a deficiency of fiber synthesis could also be responsible for the disorder²⁵. In mice a deficiency in alpha3 subunit of the neuronal nicotinic acetylcholine receptor (a mediator of normal function of the autonomic nervous system) results in similar symptoms to those of megacystis-microcolon-intestinal hypoperistalsis[26].

Sonographic findings: Megacystis-microcolon-intestinal hypoperistalsis syndrome should be considered in the presence of an abnormally distended bladder with a normal or increased amount of amniotic fluid[27]^,7,28.

Implications for targeted examinations: Dilatation of the urinary bladder in conjunction with the absence of oligohydramnios should raise the suspicion of the diagnosis, particularly in a patient at risk. It should be noted thought, that the dilatation of the bladder may not be visible in some case at the 18-20 weeks exam, and that the earliest sign maybe mild hydronephrosis³⁴.

Differential diagnosis: The main differential diagnosis is obstructive uropathy. In a female fetus, a low urinary tract obstruction can be due to urethral agenesis, variants of caudal regression syndrome, or to the rare detrusor hypertrophy. All of these cases are associated with severe oligohydramnios. Megacystis-microcolon-intestinal hypoperistalsis syndrome must be distinguished from isolated "prune belly†caused by urethral obstruction. Prune belly occurs predominantly in males, is commonly due to posterior urethral valves and has a low recurrence risk.

Associated anomalies: Omphaloceles14, cardiac malformations and multiple rhabdomyomata have been reported17^,19^,[29]. Mild webbing of the neck and intra-abdominal testis have also been associated with this syndrome14.

Prognosis: Megacystis-microcolon-intestinal hypoperistalsis syndrome is lethal in most cases, with only about 6% survivors at one year³³. An intrauterine death has been described¹². Intestinal dysfunction is the cause of death despite hyperalimentation. Septicemia has been reported as the cause of death in several infants[30]. One child has been maintained on total parenteral nutrition for 7 years[31]. But these children on long term parenteral nutrition may develop various deficiencies[32]. There are no reported cases of long term survivors.

Recurrence risk: 25%. Although most cases are sporadic, an autosomal recessive inheritance is likely since at least six pair of affected siblings and four cases where the parents were consanguineous have been reported^,,[35],1.

Management: The prognosis is poor and treatment has been shown to be ineffective. Transuterine-transfetal bladder taps have been used to relieve bladder pressure in utero[36]. Recommendations for surgical management include palliative surgery. Hyperalimentation is required. Parasympathomimetics, synthetic gastrointestinal stimulants, adrenergic blockers, and multiple gastrointestinal hormones have not been effective in inducting adequate bowel function. A cholinergic drug, bethanechol, did improve the peristalsis in one patient[37]. Partial urinary tract function may appear after bladder drainage, however, again, the intestinal dysfunction does not appear to be amenable to treatment14. Obstetrical management should include a careful search for associated anomalies. Considering the poor prognosis, pregnancy termination may be offered to the patient.

References

[1] Berdon WE, Baker DH, Blanc WA, Gay B, Santulli TV, Donovan C, Megacystis-microsolon-intestinal hypoperistalsis syndrome: a new case of intestinal hyopoeristalsis syndrome: a new case of intestinal obstruction in the newborn: report of radiologic findings in five newborn girls, Am J Roentgen 1976 126:957-964.

[2] Vezina WC, Morin FR, Winsberg F, Megacystis-microcolon-intestinal hypoperistalsis syndrome: antenatal ultrasound. AJR Am J Roentgenol 1979 Oct;133(4):749-50.

[3] Chung MY, Huang CB, Chuang JH, ko SF, Chen L, Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS): a case report.Chang Keng I Hsueh 1998 Mar;21(1):92-6 Chen CP, Wang TY, Chuang CY, Sonographic findings in a fetus with megacystis-microcolon-intestinal hypoperistalsis syndrome. J Clin Ultrasound 1998 May;26(4):217-20.

[4] Gurgan T, Zeyneloglu HY, Develioglu O, Urman B, Megacystis microcolon intestinal hypoperistalsis syndrome: antenatal ultrasound appearance. A case report. Asia Oceania J Obstet Gynaecol 1993 Dec;19(4):383-6.

[5] Shalev J, Itzchak Y, Avigad I, Hertz M, Straus S, Serr DM, Antenatal ultrasound appearance of megacystis microcolon intestinal hypoperistalsis syndrome. Isr J Med Sci 1983 Jan;19(1):76-8.

[6] Manco LG, Osterdahl P, The antenatal sonographic features of megacystis-microcolon-intestinal hypoperistalsis syndrome. JCU J Clin Ultrasound 1984 Nov-Dec;12(9):595-8.

[7] Vintzileos AM, Eisenfeld LI, Herson VC, Ingardia CJ, Feinstein SJ, Lodeiro JG, Megacystis-microcolon-intestinal hypoperistalsis syndrome. Prenatal sonographic findings and review of the literature. Am J Perinatol 1986 Oct;3(4):297-302.

[8] Young ID, McKeever PA, Brown LA, Lang GD, Prenatal diagnosis of the megacystis-microcolon-intestinal hypoperistalsis syndrome. J Med Genet 1989 Jun;26(6):403-6.

[9] Carlsson SA, Hokegard KH, Mattsson LA, Megacystis-microcolon-intestinal hypoperistalsis syndrome. Antenatal appearance in two cases. Acta Obstet Gynecol Scand 1992 Dec;71(8):645-8.

[10] Stamm E, King G, Thickman D, Megacystis-microcolon-intestinal hypoperistalsis syndrome: prenatal identification in siblings and review of the literature. JUltrasound Med 1991 Oct;10(10):599-602.

[11] Yigit S, Barlas C, Yurdakok M, Onderoglu L, Zafer Y, Saltik I ,The megacystis-microcolon-intestinal hypoperistalsis syndrome: report of a case and review of the literature. Turk J Pediatr 1996 Jan-Mar;38(1):137-41.

[12] Ferrell SA, Intrauterine death in megacystis-microcolon-intestinal hyopoeristalsis syndrome. J Med Genet 1988 25:350-351.

[13] Willard DA, Gabriele OF, Megacystis-microcolon-intestinal hypoperistalsis syndrome in a male infant. JCU J Clin Ultrasound 1986 Jul-Aug;14(6):481-5.

[14] Birth Defects Encyclopedia  Ed. Buyse ML, Blackwell Scientific Publications, Cambridge, MA 02142 P. 978-9.

[15] Krook PM, Megacystis-microcolon-intestinal hypoperistalsis syndrome in a male infant. Radiology 1980 Sep;136(3):649-50.

[16] Puri P, Lake BK, Gorman F, O’Donnell B, Nixon HH: Megacystis-microcolon-intestinal hypoperistalsis syndrome: a visceral myopathy. J Pediat Surg 1983 18:64-69.

[17] Patel R, Carty H, Megacystis-microcolon-intestinal hypoperistalsis syndrome: a rare cause of intestinal obstruction in the newborn. Brit J Radiol 1980 53:249-252.

[18] Oliveira G, Boechat MI, Ferreira, MA: Megacystis-microcolon-intestinal hypoperistalsis syndrome in a newborn girl whose borther had prune belly syndrome: common pathogenesis? Pediat Radiol 1983 13:294-296.

[19] Winter RM, Knowles SAS: Megacystis-microcolon-intestinal hypoperistalsis syndrome: confirmation of autosomal recessive inheritance. J Med Genet 1986 23:360-362.

[20] McNamara HM, Onwude JL, Thornton JG, Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report supporting autosomal recessive inheritance. Prenat Diagn 1994 Feb;14(2):153-4

[21] Srikanth MS, Ford EG, Isaacs H Jr, Mahour GH Megacystis microcolon intestinal hypoperistalsis syndrome: late sequelae and possible pathogenesis. J Pediatr Surg 1993 Jul;28(7):957-9

[22] Chung MY, Huang CB, Chuang JH, Ko SF, Chen L Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS): a case report. Chang Keng I Hsueh 1998 Mar;21(1):92-6

[23] Ozok G, Erdener A, Herek O, Tuncyurek M, Alkanat M, Gokdemir A Microcolon-intestinal hypoperistalsis without megacystis: uncommon form of neonatal intestinal pseudoobstruction. Eur J Pediatr Surg 1995 Apr;5(2):124-7

[24] al-Rayess M, Ambler MW Axonal dystrophy presenting as the megacystis-microcolon-intestinal hypoperistalsis syndrome. Pediatr Pathol 1992 Sep-Oct;12(5):743-50

[25] Ciftci AO, Cook RC, van Velzen D Megacystis microcolon intestinal hypoperistalsis syndrome: evidence of a primary myocellular defect of contractile fiber synthesis. J Pediatr Surg 1996 Dec;31(12):1706-11

[26] Xu W, Gelber S, Orr-Urtreger A, Armstrong D, Lewis RA, Ou CN, Patrick J, Role L, De Biasi M, Beaudet AL

Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A 1999 May 11;96(10):5746-51

[27] Deutinger J, Bernaschek G, Gherardini G, Schatten C Fetal megacystis--prenatal diagnosis and attempt at therapy. Z Geburtshilfe Perinatol 1986 Jul-Aug;190(4):168-71

[28] Prenatal Diagnosis of Congenital Anomalies, Eds. Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins J Appleton & Lange1988 East Norwalk, CT 06855 p 291.

[29] Couper RT, Byard RW, Cutz E, Stringer DA, Durie PR: Cardiac rhabdomyomata and megacystis-microcolon-intestinal hypoperistalsis syndrome. J Med Genet 1991 28:274-276.

[30] Kupferman JC,