Address correspondence to: Keith A. Aqua, MD, University of Arizona, Dept. of Obstetrics and Gynecology, 1501 North Campbell Avenue, Tucson, Arizona 85724-0001, Ph: 602-626-6636 Fax 602-626-2514.

Synonyms: Eagle-Barret syndrome and triad syndrome (absence of abdominal muscles, with urinary tract abnormality and cryptorchidism).

Definition: Prune-Belly syndrome (PBS) describes the triad of dilation of the urinary tract, a deficiency of the abdominal wall musculature, and failure of testicular descent.

Prevalence: 0.2-0.3:10,000 live births, M20:Fl.

Etiology: Presently undetermined. The complex nature of this syndrome has led to considerable speculation about its etioloqy and pathogenesis, including primary obstructive urinary anomalies, defective mesodermal development, intrauterine viral illness, and genetic factors. Although a genetic basis has not been established, cases have been documented in siblings and twin gestations.

Differential diagnosis: Megacystis-microcolon-intestinal hypoperistalsis syndrome, enteric duplication cyst, urachal cyst, ureteropelvic junction obstruction, posterior urethral valve syndrome, bladder extrophy, and ascites (Table 1).

Prognosis: There is a wide spectrum of severity with this syndrome. Survival is related to renal and pulmonary function. If complete urinary obstruction exists leading to severe bilateral renal dysplasia, oligohydramnios, and pulmonary hypoplasia, then prognosis is dismal.

Recurrence risk: Not increased.

Management: Based on fetal sonographic findings consistent with distal urinary tract obstruction. In selected cases, in utero decompression and urinary diversion may allow sufficient renal and pulmonary development to permit the fetus to survive after birth.

MESH Prune-Belly syndrome ICD9 756.7 BDE 2007 CDC 756.720 MIM 100100 POS 3003

Introduction

The classical triad of urinary tract anomalies, deficient abdominal musculature, and bilateral cryptorchidism describes the Prune-Belly syndrome. In addition to this classic triad, a broad spectrum of associated defects including musculoskeletal, cardiovascular, pulmonary, and genital malformations have been documented^1-2. When the urinary tract maldevelopment is associated with severe obstructive uropathy, this syndrome can lead to oligohydramnios and pulmonary hypoplasia. Several reports exist documenting the success of urinary tract decompression in the presence of severe oligohydramnios^3-6. This case report describes the outcome of a fetus with Prune-Belly syndrome and severe oligohydramnios who underwent urinary tract diversion through the use of a vesicoamniotic shunt.

Case report

A 25-year-old G₃P_l was transferred to the authors" facility after a routine sonogram during early gestation revealed a fetal cystic mass in the abdomen. Subsequent ultrasound revealed fetal megacystis, bilateral hydronephrosis with echogenic renal parenchyma, normal amniotic fluid volume and a fetus consistent with 15 weeks (figs. 1,2).

Figure 2: Sagittal plane of the fetus at 16 weeks gestation: B, bladder; small arrow, heart; large arrow, fetal cranium.

The remainder of the targeted fetal survey was unremarkable. Despite the dismal prognosis associated with presumed obstructive uropathy, the patient subsequently underwent amniocentesis and vesicocentesis. Chromosome analysis revealed a normal male karyotype, and fetal urine electrolytes were suggestive of renal function. One week later an ultrasound revealed an enlarging bladder impinging on intrathoracic structures and a decreased amniotic fluid volume. With declining amniotic fluid, thoracic compression, and urine electrolytes consistent with persistent renal function, a fetal vesicoamniotic shunt was placed. Under ultrasound guidance, approximately 150-200cc of fetal urine was drained as a 1.5mm double-pigtail catheter was placed into the fetal bladder through a #14 gauge trocar (figs. 3-4).

Figure 3: Ultrasound- guided percutaneous placement of the vesicoamniotic needle in position (arrow).

Three days following the procedure, sonography revealed a properly placed shunt with moderate fetal ascites. One week following the procedure, the amniotic fluid index (AFI) had increased to 10 cm and there was no change in the dilatation of the renal pelves (left 1.5 cm, right 1.6 cm). The remainder of this patient"s prenatal course was essentially unremarkable, and ultrasound evaluation every one to two weeks for interval growth revealed normal amniotic fluid indices. Ultrasound at 34 weeks demonstrated an AFI of 130 mm with the left renal pelvis 18 mm and the right renal pelvis 13 mm (fig. 5).

At 36 weeks the patient was induced secondary to an inability to visualize the shunt, and there was a slight increase in the size of the left renal pelvis. A 2715g live-born male was delivered vaginally without complication. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. The neonate"s abdomen was distended and wrinkled, with a bladder palpable 3 cm above the umbilicus. No testes were palpable. The extremities were without abnormality. Neonatal echocardiography was normal. A renal ultrasound revealed moderate bilateral hydronephrosis along with significant ureteral dilatation. An abdominal radiograph revealed an asymmetric abdomen, suggesting congenital herniation and 13 ribs. A voiding cystourethrogram revealed a large oval-shaped distended bladder with marked bilateral grade IV vesicoureteral reflux and no evidence of posterior urethral valves. In addition, the distal urethra was distended. Neonatal creatinine was 0.5 mg/dl, and on discharge from the hospital it was 0.2 mg/dl. This neonate has Prune-Belly syndrome. At nine months of age, the infant is doing well with ureteral reimplantation and repair of his cryptorchidism.

Discussion

This case illustrates the diagnosis of Prune-Belly syndrome at 15 weeks gestation.

Etiology

A variety of malformations other than Prune-Belly syndrome may account for urethral level obstruction, including posterior urethral valves, urethral stenosis, and urethral atresia. Distal urinary tract obstruction can produce a broad spectrum of antenatal sonographic features, depending on both the duration and the degree of obstruction⁷.

Pathogenesis

The embryological defect that is responsible for Prune-Belly syndrome is still not known. The mesodermal defect theory suggests that a defect exists in the mesoderm of the anterior abdominal wall and urinary tract (figs. 6,7).

Figure 7: Transverse section through the embryo caudal to the previous section at 26 days of gestation, The intermediate mesoderm in the sacral region forms a solid, unsegmented mass of tissue, the nephrogenic cord. The urogenital ridges are produced by these nephrogenic cords.

Between 6 and 10 weeks of gestation, aberrant development of the derivatives of the first lumbar myotome lead to a patchy muscular deficiency or hypoplasia of the abdominal wall as well as to urinary tract abnormalities (fig. 8)¹⁰. In no cases are the muscles congenitally absent^1,11-14. Similarly, Straub¹⁵ favors the concept that Prune-Belly syndrome is a generalized developmental abnormality in which individual manifestations of the syndrome occur as a result of a "disturbed inductor-to-organizer cell-cell interaction" during early embryogenesis. The abnormality is thought to be in the splanchnic mesoderm lateral to the notochord from which most of the abdominal wall and genitourinary system originate.

An alternate theory, the urethral obstruction malformation complex, proposes that pressure atrophy of the abdominal wall muscles occurs when urethral obstruction leads to massive distention of the bladder and ureters. Bladder distention would also interfere with descent of the testes and thus be responsible for the bilateral cryptorchidism. The mechanism responsible for the urinary tract dilatation and distention is a flap valve mechanism that results from a hypoplasia of the stromal and epithelial elements of the prostatic urethral^l-12. The hypoplasia of these elements leads to an underlying weakness and subsequent sacculation of the prostatic urethra.

Table 1: Differential diagnosis of Prune-Belly syndrome.

n Megacystis-microcolon-intestinal hypoperistalsis syndrome

n Posterior urethral valve syndrome

n Ureteropelvic junction obstruction

n Bladder exstrophy

n Urachal cyst

n Enteric duplication cyst Ascites

Table 2: Sonographic findings of Prune-Belly syndrome.

n Persistent megacystis

n Persistent dilatation of the proximal urethra

n Thickening of the bladder wall in the setting of oligohydramnios

Table 3: Associated sonographic findings consistent with urethral level obstruction

n Oligohydramnios

n Hydroureter

n Pyelocaliectasis

n Urinary ascites or a paranephric urinoma

n Renal cortical cyst

Incidence

The higher incidence of this syndrome in males has been explained on the basis of the more complex morphogenesis of the male urethra, possibly resulting in obstructive anomalies at several levels. Prune-Belly syndrome is rare in females, with fewer than 30 cases reported in the literature¹⁴.

Diagnosis

An ultrasound examination that reveals a dilated bladder and/or fetal ureters, a distended fetal abdomen, and oligohydramnios, either alone or in combination, should alert a physician to the possibility of Prune-Belly syndrome⁸.

Chronic obstruction of the fetal urinary tract can lead to renal dysplasia or macroscopic parenchymal cyst formation⁷. Nyberg⁹ described the cardinal sonographic features consistent with urethral level obstruction (Table 1). The diagnostic criteria in this case were confirmed by the massively dilated fluid-filled structure arising from the fetal pelvis, the bilateral tortuous and dilated ureters, the bilateral caliectasis, the echogenic renal parenchyma, and worsening oligohydramnios.

Differential diagnosis

Differential diagnosis are listed in Table 2.

Recurrence

A familial occurrence has been seen in some affected patients, suggestive of an X-linked inheritance^{l 6}. A multifactorial, or polygenic, inheritance has also been proposed. Additionally, areas of Nigeria have a high prevalence of Prune-Belly syndrome.

Associated anomalies

There are a variety of nonurologic problems present in individuals with Prune-Belly syndrome (Table 3). Musculoskeletal malformations are present 20-60% of the time. The most common abnormalities are talipes deformities, congenital hip dislocation, and clubbed feet¹¹. Pectus excavatum, polydactyly, and flared iliac wings have also been reported^l. Gastrointestinal anomalies such as intestinal malrotation, imperforate anus, and anal atresia are seen in 30-40% of individuals with Prune-Belly syndrome^1,2,11. Pulmonary anomalies are common, the most severe of which is hypoplasia of the lungs secondary to oligohydramnios. Cardiovascular malformations have been documented in 10% of patients and include septal defects and patent ductus arteriosus^1,2,11.

Management

The ability to diagnose birth defects antenatally has improved considerably with high resolution sonography. Although many fetal abnormalities can now be diagnosed, the potential for active fetal therapy exists for only a few patients.

Anatomic abnormalities that warrant consideration of correction are those that interfere with critical fetal organ development. Experimental evidence suggests that fetal urinary tract obstruction, whether intermittent or persistent, can lead to renal dysplasia, which is often irreversible, even if the obstruction is relieved immediately after birth⁶. The fetus with urinary tract obstruction and oligohydramnios has a poor prognosis. The percutaneous placement of an indwelling catheter for urinary diversion is one possible therapy. Urinary tract decompression in the early second trimester is desirable to reduce the potential for ongoing damage to the developing kidneys. Additionally, correction of severe oligohydramnios as early as possible should reduce the possibility of pulmonary hypoplasia.

Repeated aspiration of the fetal bladder might not effectively decompress the bladder and upper urinary tract. This decompression has successfully been accomplished with the insertion of an indwelling vesicoamniotic shunt for drainage of the fetal bladder^4-7,17. Suprapubic drainage of urine from the bladder into the amniotic fluid should allow renal development to proceed and restore normal amniotic fluid dynamics. The benefits of such therapy remain controversial and are yet to be evaluated in a prospective, randomized fashion. As such, urinary diversion should be considered on a case-by-case basis.

Neonatal management

The neonatal findings of a redundant abdominal wall and bilateral cryptorchidism should prompt a complete diagnostic evaluation for Prune-Belly syndrome. The urinary tract should be evaluated radiographically with both an abdominal/pelvic ultrasound and a voiding cystourethrogram. A blood urea nitrogen (BUN), creatinine (Cr), and serum electrolytes should be obtained for a baseline and followed carefully during the first week of life. A rising BUN and Cr during the first week suggests a poor prognosis for normal renal function¹⁸. The primary role of treatment in the neonate is the preservation of renal function. This is carried out primarily with prophylactic antibiotics to prevent pyelonephritis and surgical relief of obstruction when present. Because of the risk of testicular malignancy, orchiopexy should be performed. This may be performed in a 1 or 2-stage procedure; whether this is performed in the neonatal period or early childhood is controversial¹². Abdominal wall reconstruction for both aesthetics and function is often necessary. Because 75% of individuals with Prune-Belly syndrome have extraurinary anomalies, a thorough evaluation, especially cardiac, should be performed.

Prognosis

Although many ethical questions are raised when innovative fetal therapy is discussed, the insults that result from urinary tract obstruction often lead to stillbirth or neonatal death. Outcome is typically good in cases of Prune-Belly syndrome with normal amniotic fluid volume. The appearance of severe oligohydramnios, or anhydramnios, and bilateral echodense renal parenchyma carries a very poor prognosis regardless of etiology. These neonates succumb from pulmonary hypoplasia in the first hours of life or from renal failure in the first days of life. Poor prognostic indicators include oligohydramnios, a large amount of urinary ascites, a dystrophic bladder, and peritoneal calcifications¹⁹. Prognosis may be improved with urinary tract decompression, Although urinary diversion with an indwelling suprapubic catheter is currently viewed as innovative therapy, the results obtained in this and other cases suggest that it may be worthwhile to pursue in selected cases.

References

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2. Manivel JC, et al: Prune-Belly syndrome: clinicopathopathologic study of 29 cases. Pediatr Pathol 9:691-711, 1989.

3. Harrison MR et al: Fetal surgery for congenital hydronephrosis. N Eng J Med 306:591-593, 1982.

4. Harrison MR, Filly RA, Parer JT, et al: Management of the fetus with a urinary tract malformation. JAMA 246:635-9, 1981.

5. Harrison MR, Golbus MS, Filly RA: Management of the fetus with a correctable congenital defect, JAMA 246:774-777, 1981.

6. Glick PL, Harrison MR, Adzick NS, et al: Correction of congenital hydronephrosis in utero IV: In utero decompression prevents renal dysplasia. J Ped Surg 19:649-657, 1984.

7. Glazer GM, Filly RA, Callen PW: The varied sonographic appearance of the urinary tract in the fetus and newborn with urethral obstruction. Radiology 144:563-568, 1982.

8. Shih WJ, Greenbaum LD, Baro C: In utero sonoqram in Prune-Belly syndrome. Urology XX:102-105, 1982.

9. Nyberg DA, Mahony BS, Pretorius DH: Diagnostic ultrasound of fetal anomalies: text and atlas, Year Book Medical Publishers, 1990.

10. Moore KL: The Developing Human: Clinically oriented embryology. W.B. Saunders Company, 1988.

11. Greskovich FJ, Nyberg LM: The Prune-Belly syndrome: a review of its etiology, defects, treatment, and prognosis. J Urol 140:707-712, 1988.

12. Romero R, Pilu GL, Jeanty P, et al: Prenatal diagnosis of congenital anomalies. Appleton & Lange,1988.

13. Pinto T, Baithun SI, Giwan YA, et al: The Prune-Belly syndrome - a possible pathogenesis. Diagn Histopathol 5:197-203, 1982.

14. Reinberg Y, et al: Prune-Belly syndrome in females: a triad of abdominal musculature deficiency and anomalies of the urinary and genital systems. J Pediatr 118:395-398, 1991,

15. Straub E, Spranger J: Etiology and pathogenesis of the Prune-Belly syndrome. Kidney Int 20:695-699, 1981.

16. Nakayama DK, Harrison MR, Chinn DH, et al: The pathogenesis of Prune-Belly, Am J Dis Child 138:834-836, 1984.

17. Golbus MS, Harrison MR, Filly RA, et al: In utero treatment of urinary tract obstruction. Am J Obstet Gynecol 142:383-388, 1982,

18. Seeds JW, Azizkhan RG: Congenital malformations, antenatal diagnosis, perinatal management, and counseling. Aspen Publishers, Inc., 1990.

19. Mahony BS, Callen PW, Filly RA: Fetal urethral obstruction: US evaluation. Radiology 157: 221-224, 1985.