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The Turkish Journal of Pediatrics 2008; 50: 269-274 Case

An antenatal appearance of megacystis-microcolon-intestinalhypoperistalsis syndrome

Yoichiro Oka1,2, Koushi Asabe1,2, Takayuki Shirakusa1, Kazuki Nabeshima31Division of Pediatric Surgery,Department of Surgery, Fukuoka University School of Medicine, and 2Maternity andPerinatal Care Center and 3Department of Pathology, Fukuoka University Hospital, Fukuoka, Japan

SUMMARY: Oka Y, Asabe K, Shirakusa T, Nabeshima K. An antenatalappearance of megacystis-microcolon-intestinal hypoperistalsis syndrome. Turk

J Pediatr 2008; 50: 269-274.

We herein present a megacystis-microcolon-intestinal hypoperistalsis syndrome(MMIHS) case followed by ultrasound (US) examinations before birth.

During the prenatal US examination of a 34-year-old woman, an enlarged

bladder with bilateral hydronephrosis and hydroureter of the fetus weredetected. The amniotic fluid was normal in the second trimester butpolyhydramnios was observed in the third trimester.

A female baby was born by cesarian section weighing 2632 g. Imaging studiesdetected an enlarged bladder with bilateral hydronephrosis, hydroureter andmicrocolon. Laparotomy on the 9th day confirmed a short small bowel withcaliber change and the existence of ganglion cells and plexus of the nervein the intestine. These findings correlated with the previously reportedcharacteristics of MMIHS.

An enlarged bladder in the second trimester and polyhydramnios in the thirdtrimester have been reported in many cases of MMIHS. These findings maythus help to accurately diagnose MMIHS before birth.

Key words: megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS),antenatal diagnosis.

Megacystis-microcolon-intestinal hypoperistalsissyndrome (MMIHS) was reported for the firsttime in 1976 by Berdon et al.1, and it isdefined as a functional intestinal obstructioncharacterized by microcolon, non-obstructivebladder distension, and a decreased or absent

peristalsis of bowel. It is a rare autosomalrecessive disorder and differs from Hirschsprungdisease with its mature ganglion cells and nerveplexuses in the intestinal wall. MMIHS is morelikely to develop in female infants and to becomecomplicated with microcolon and malrotation.

We herein present a case suspected as MMIHSbefore birth and also discuss the findings of MMIHSbased on prenatal ultrasound examination.

Case Report

A 34-year-old woman, primigravida, was referredto our institution at 25 weeks of gestation for

l i f l bl dd di d b

a routine ultrasound examination at 23 weeksof gestation at another hospital. The prenatalcourse was otherwise unremarkable.

The first ultrasound evaluation in our Obstetricsand Gynecology (OB-GYN) Departmentrevealed a large bladder measuring 506056

mm (estimated volume 90 cm2), bilateralhydronephrosis with right renal pelvis measuring121315 mm and a left renal pelvis measuring131717 mm (Fig. 1). At 31 weeks ofgestation, ultrasound-guided bladder puncturewas performed and 175 ml of urine wasaspirated. An analysis of the urine showedNa 45 mEq/L, Cl 41 mEq/L, and osmolarity112 mOsm/L. After aspiration, the bladder wasatonic without contraction (6 hours later therefilling of urine was confirmed by an ultrasoundexamination) and a distended stomach was alsofound (Fig. 2). Non-ionic contrast material wasinjected into the bladder but no ureters couldb i li d bil ll l i

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production with no vesicoureteral reflux (VUR)

was thus confirmed. In addition, the amountof amniotic fluid was normal.

At 37 weeks of gestation, she was admittedto the OB-GYN Department with a diagnosisof a premature rupture of the membrane.By ultrasound examination at admission, theestimated weight was 3630 g; the bladdermeasured 1078084 mm, right renalpelvis 312636 mm, and left renal pelvis384056 mm. Because of hydramnios,1300 ml of amniotic fluid was aspirated. At37 weeks and 3 days of gestation, the patientunderwent a primary cesarean section afterinduction failure because fetal distress was

d Th i f f l i hi

Fig. 1. Sections through the fetal abdomen. a: coronal

section. b: transverse section. c: sagittal section.K: Kidney. B: Distended bladder.

Fig. 2. Sonogram after bladder puncture.S: Distended stomach. K: Kidney.

2632 g, with Apgar scores of 8 and 9 at 1 and5 minutes, respectively. She was admitted tothe Neonatal Intensive Care Unit (NICU) foran evaluation of large bladder and bilateral

hydronephrosis.The physical examination in the NICU showeda normally developed 37-week gestation infant(no visible findings of external malformation,no distended abdomen), except for the presenceof a somewhat less audible intestinal sound.

After spontaneous micturition (89 ml) wasseen, the first ultrasound examination wasperformed. The bladder was remarkablydistended and bilateral hydronephrosis andhydroureters were also seen. The expansion of

the right renal pelvis and ureter was severe.A gastric tube was inserted to treat gastricdistension. The chest-abdominal X-ray the nextday showed a distended stomach with littlemovement of intestinal tract gas. On the 7thday after birth, a view of microcolon wasconfirmed by a contrast enema while an uppergastrointestinal (GI) series demonstrated anatonic distended stomach and little passageof contrast media from the stomach to theduodenum (Fig. 3).

On the 9th day, a laparotomy was performed.Inspection of the total intestinal tractdemonstrated absence of Treitz ligament withno Ladd band and ileocecal region located onright upper quadrant, which thus indicatednon-rotation type malrotation. The small

Fig. 3. A contrast enema demonstrated microcolon and

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Fig. 4. A ganglion cell is detected (arrow) inhistopathological examination of the muscle layers of

the intestinal specimens.

intestine was short, at 70 cm, and had caliberchange at the point of 40 cm from the endof the duodenum. The presence of microcolonwas also confirmed. An intraoperative frozen-

paraffin inspection of full-thickness specimenat the point of caliber change of the smallintestine was done to rule out Hirschsprungdisease, and the existence of ganglion cellsand the plexus of the nerve was confirmed(Fig. 4). A double lumen jejunostomy was thusperformed at the point of caliber change andbiopsy of ascending colon and appendectomywere also done.

Pathological inspection after the operationconfirmed the Auerbach nerve plexus andganglion cells were in the proper positionof specimens of the vermiform appendix andascending colon. Numerous S-100 protein-positive cells were recognized and wereregarded as Schwann cells.

After operation, in addition to total parenteralnutrition (TPN), oral feeding was initiated.

The increased oral intake, however, inducedan increase in intestinal juice from the

jejunostomy, thus causing dehydration andweight loss. As a result, an adjustment of the

l k f d d

A balloon catheter was inserted after admittanceto NICU. Intermittent urinary catheter insertionhad been initiated at one week of age. Theurinary volume and renal function had been kept

normal without episode of urinary tract infection(UTI) for two months. However, the firstepisode of UTI appeared and antibiotic therapywas thus initiated. As left pyonephrosis hadbeen detected by both ultrasound examinationand a computerized tomography (CT) scan, leftnephrostomy was made. Left ureteropelvic junctionstenosis was suspected by pyeloureterography,and pyeloureteroplasty was performed at sevenmonths of age. The passage of urine from eachkidney to its ureter was confirmed by intravenouspyelography (IP) after the operation.

The long-term intravenous hyperalimentation(IVH) and frequent episodes of infectiousdiseases such as catheter sepsis and UTIcaused a progression of liver dysfunction. Thesymptoms of multi-organ failure includingpulmonary edema, liver failure, and portalhypertension had appeared after the episodeof infection in the subdermal implant portfor IVH at 1 year 6 months of age. Therepeated episodes of upper and/or lower GIbleedings induced by portal hypertension couldnot be controlled by attempts of endoscopicsclerotherapy. As a result, the condition of thepatient worsened. The patient was transferredto another institution at 1 year 10 months ofage in order to prepare for a transplant of theliver and small intestine, but the scheduledtransplant could not be performed due to thepatients poor condition and she died at twoyears of age.

Discussion

Megacystis-microcolon-intestinal hypoperistalsissyndrome (MMIHS) is a rare disordercharacterized by a remarkable decrease inperistalsis of the intestinal tract. The patientcannot take appropriate oral feeding andtherefore is required to undergo long-term

TPN. Most children with MMIHS tend to dieof complications related to TPN, includingcatheter sepsis or liver failure, etc. Althougha few long-term survivors of MMIHS havebeen reported2,3 due to recent progress in themanagement of TPN, such patients still cannottolerate full oral intake and therefore TPNcannot be discontinued. MMIHS is one of the

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prognosis remains poor at the present time.Establishing a prenatal diagnosis of MMIHSas early as possible using antenatal ultrasoundexaminations may help not only the physicians

but also the parents in selecting and preparingthe appropriate treatment.

Since Penman et al.4 first described theirfindings of fetal ultrasound examinations ofMMIHS in 1989, there have only been a fewfindings of fetal ultrasound examinations ofMMIHS in the literature and thus standard ofdiagnosis is still unclear.

In our case, the findings of an enlarged bladderwith bilateral hydronephrosis and hydroureterwere determined on ultrasound examination

in the second trimester of pregnancy and anabsence of VUR was confirmed by transuteralcystoradiogram. The renal function and urineproduction of the fetus were normal basedon an analysis of fetal urine. The volumeof amniotic fluid was normal. In the thirdtrimester, the findings of distended stomachand polyhydramnios were detected.

The diseases that show an enlarged bladder inthe second trimester can be divided into twocategories, consisting of obstructive and non-

obstructive urethral diseases. Post urethral valve(PUV) in males and urethral atresia in femalesare considered to be obstructive urethral disease,whereas neurogenic bladder, severe VUR withouturethral atresia as well as MMIHS are thoughtto be non-obstructive disease. The amount ofamniotic fluid in patients with obstructive urethraldisease tends to be normal in the second trimesterof pregnancy but oligohydramnios is seen in thethird trimester of pregnancy22,23. Other findingssuch as VUR, hydronephrosis, and hydroureterare also seen in obstructive urethral disease. Thefinding of increased renal echogenicity relativeto the neighboring liver parenchyma in suchobstructive urethral disease because of injury tothe renal cortex by high pressure to the urinarytract has also been reported22,24.

As for non-obstructive urethral disease, thereis a male predominance regarding the incidencein severe VUR, whereas MMIHS has a femalepredominance. Although hydronephrosis andhydroureter are seen in both disorders, VURis not seen in MMIHS12.

We reviewed the pertinent literature to obtainrelated findings regarding ultrasound examination

f S4 22 d h id ifi d 22

(including our case) (11 boys and 11 girls).According to their gestation period, birthweight, and Apgar score (with the exceptionof cases whose details were unknown or cases

terminated), almost all were full-term babies andasphyxia at birth was rare (Table I).

The prenatal findings of MMIHS are summarizedin Table II. Although MMIHS is a disorderwith morphological and functional anomaliesboth of the intestinal and urinary tract system,abnormal findings of the urinary tract systemsuch as bladder distension, hydronephrosisand hydroureter were more frequent thanthose of the intestinal tract system such asa distended stomach or intestine. The former

were detected in the second trimester whereasthe latter were detected in the third trimesterof pregnancy in many cases. Regarding theamount of amniotic fluid, many cases showeda normal volume in the second trimester ofpregnancy but polyhydramnios in the lasttrimester of pregnancy.

Polyhydramnios is one of the most commonfindings in MMIHS cases. One previous studydescribed polyhydramnios as present in morethan 90% of all MMIHS cases25. In MMIHS

cases, the findings of an enlargement of thestomach and intestine seen in the secondand third trimesters of pregnancy are inducedby a functional obstruction of the digestivetract. Therefore, many cases of MMIHS hadpolyhydramnios because of an ineffectiveabsorption induced by a decreased functional

Table I. Characteristics of MMIHS CasesDiagnosed Prenatally

No. of cases

22 (21 cases from literatures and

present case)

SexMaleFemale

1111

Gestation* 36.92.0 weeks (3240 weeks)

Birth weight* 3106.3678.1 g (17704280 g)

Apgar score1 minute 7.21.9 (46)

5 minutes 8.41.3 (610)

PrognosisTermination

AliveDeathUnknown

2

5132

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Table II. Prenatal Ultrasound Findings of MMIHS

1st trimester(015W)

2nd trimester(1627W)

3rd trimester(28W) Total

Urinary tractEnlarged bladderHydronephrosis or hydroureter

1310

72

2012

Amount of amniotic fluidOligohydramniosNormalPolyhydramnios

181 6

187

Digestive tractDistended stomachDistended intestine

31

12

43

peristalsis of the digestive tract between the

second and third trimester of pregnancy,whether or not impaired urine production ofthe fetus actually existed26.

Cases of sibs among MMIHS patients have beenreported6,10,27. There were two cases in whichselective termination was chosen, as seen in

Table II. The mother of one case had a previoushistory of delivering a baby with a diagnosisof MMIHS. Some studies had reported MMIHSto be an autosomal recessive disease4,27.

In conclusion, findings of an enlarged bladder

with hydronephrosis in the second trimesterof pregnancy and polyhydramnios in the thirdtrimester of pregnancy were reported in manycases of MMIHS. The combination of theseprenatal findings and a previous history ofdelivery of a baby with MMIHS thereforesuggest a diagnosis of MMIHS before birth.

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