Pediatrics: Prune-Belly Syndrome

Epidemiology

• Incidence: 1 in 29,000-40,000 live births, similar to that of bladder exstrophy
• 95% of cases occur in males

Genetics

• Most have a normal karyotype
  • An associated chromosomal abnormality is the exception rather than the rule

Diagnosis and Evaluation

• Clinical Features
  • Broad spectrum of severity, with some children not surviving the newborn period and others being minimally affected
  • The most important determinant of long-term survival is usually the severity of the urinary tract anomaly, in particular, the degree of renal dysplasia
  • Major findings of PBS (3):
    1. Deficiency of the abdominal musculature
    2. Bilateral intra-abdominal testes
    3. Genitourinary anomalies

Genitourinary Anomalies

1. Kidneys
   • Non-obstructive hydronephrosis is the rule
     • Collecting system is characteristically dilated, often to a severe degree, however, the calyceal morphology may be well preserved
     • The degree of dilation does not correlate with the degree of renal dysplasia
2. Ureters
   • Dilated and tortuous
   • Ureteral dysfunction is related to:
     • Ureteral dilatation with failure of luminal coaptation during peristalsis
     • Reduced smooth muscle tissue and increased amount of fibrous connective tissue
     • Failure of propagation of an electrical conduction due to increased fibrous connective tissue.
     • Abnormal myofilament content in smooth muscle cells
   • The most normal portion of the ureter with the greatest amount of smooth muscle is in the proximal segment. This is the segment that should be preserved for reconstruction.
   • Vesicoureteral reflux is present in 75% of children
3. Bladder
   • Usually massively enlarged with a pseudodiverticulum at the urachus
   • Urachus is patent at birth in 25-30% of children  
   • Wide bladder neck opening into a dilated prostatic urethra
   • Usually, urodynamics reveals
     • Excellent detrusor compliance; the end-filling pressure assumes a normal value; and the bladder functions well as a reservoir.
     • Delayed first sensation to void, and bladder capacity may be more than double the normal volume.
     • Presence of vesicoureteral reflux and reduced detrusor contractility.
   • ≈50% patients void spontaneously with normal voiding pressures, normal flow rates, and low postvoid residuals
4. Prostate and Accessory Sex Organs
   • Prostatic hypoplasia
     • Thought to be a factor in the ejaculatory failure of PBS patients
     • Dilation of the posterior urethra is caused by prostatic hypoplasia and results in retrograde ejaculation
   • The vas and seminal vesicles are often atretic.
5. Anterior urethra
   • Most common anterior urethral anomalies:
     • Urethral atresia
     • Hypoplasia and megalourethra
       • The fusiform type of megalourethra involves deficiencies of the corpus cavernosum and corpus spongiosum, whereas the scaphoid variety involves a deficiency of corpus spongiosum only.
6. Testes
   • Bilateral intra-abdominal testes lying over the iliac vessels and adjacent to the dilated ureters are the most typical findings
   • No difference in germ cell counts, Ad spermatogonia, and Leydig cells between PBS testes and non-PBS intra-abdominal testes
     • This implies that the environmental state of the abdomen is a major factor in their later spermatogenic potential

Extra-genitourinary Abnormalities

1. Abdominal Wall Defect
   • The inferior and medial segments are the most consistently affected
2. Cardiac Anomalies
   1. Patent ductus arteriosus
   2. Atrial septal defect
   3. Ventricular septal defect
   4. Tetralogy of Fallot
3. Pulmonary
   • Pulmonary hypoplasia
     • Can result from severe oligohydramnios related to renal dysplasia or severe bladder outlet obstruction
   • Pneumomediastinum
   • Pneumothorax
   • Pneumonia and lobar atelectasis
4. Gastrointestinal abnormalities
   • Increased bowel mobility with intestinal malrotation, volvulus, atresias, and stenosis

• It is exceptionally rare to encounter a normal urinary tract in association with the characteristic abdominal wall defect in a male. However, the converse is not unusual. Some patients (with pseudo-prune-belly syndrome) with a normal or relatively normal abdominal wall exhibit many or all of the internal urologic features. These features may include dysplastic or dysmorphic kidneys or dilated and tortuous ureters

Prenatal Diagnosis

• Prenatal US may demonstrate:
  1. Hydronephrosis
     • Can be diagnosed accurately in the second trimester and is present in ≈1% of all pregnancies
  2. Enlarged bladder
  3. Ascites presenting in the second trimester
  4. Irregular abdominal wall circumference
  • Although external genital anomalies such as bilaterally undescended testes and megalourethra occur with prune-belly syndrome, these would not be detected on prenatal ultrasound as abnormalities of external genital development.

Female Syndrome

• 5% of PBS patients are female
• Females with PBS exhibit the abdominal wall deficiency and urinary tract dysmorphism without any gonadal anomaly

Management

Pre-natal

• The most appropriate indication for prenatal intervention in suspected prune-belly syndrome is urethral atresia and progressive oligohydramnios
  • The only situation with prune-belly syndrome that is potentially reversible is the pulmonary hypoplasia that is seen from urethral atresia and due to progressive oligohydramnios.
  • Oligohydramnios that occurs early in the second trimester is generally indicative of severe renal dysplasia.
  • Oligohydramnios, hydronephrosis, pulmonary hypoplasia, distended bladder, and urinary ascites do not independently warrant prenatal intervention
    • Hydronephrosis in prune-belly syndrome is well tolerated

Neonates

• A neonatology, nephrology, cardiology, and urology team is necessary
  • Other associated abnormalities, such as cardiac or pulmonary, often take precedence over the urinary tract
    • Pulmonary complications are most likely to threaten the early survival
      • Immediate CXR is necessary to exclude commonly associated pulmonary abnormalities
    • Early urologic intervention is indicated only for neonates with evidence of bladder outlet obstruction (e.g. urethral atresia), preferably with a percutaneous suprapubic tube while the newborn is in the neonatal intensive care unitI
• After stabilization, urologic evaluation proceeds with:
  • History and physical examination
  • Labs
    • Serum creatinine, BUN and electrolytes
      • Assess for the potential systemic acidosis and electrolyte imbalances that may be seen in renal insufficiency
  • Imaging
    • Ultrasound
    • VCUG
      • Should be avoided to reduce unless potential for introduction of bacteria from catherization unless the results are necessary for immediate clinical decision making.
        • Necessary in neonates with renal insufficiency to rule out as the etiology bladder outlet obstruction versus urinary stagnation
      • Prophylactic antibiotic therapy is recommended, especially before urinary tract instrumentation, including the initial VCUG
        • Once bacteria are introduced, infection in a static system may be difficult to eradicate.
• Reconstruction is best delayed until the child is approximately 3 months old, to allow for pulmonary maturation.
  • Early retailoring of the urinary system to reduce stasis and eliminate reflux or obstruction has included ureteral shortening, tapering and vesicoureteral reimplantation, and reduction cystoplasty.
• Surgical reconstruction
  1. Circumcision
     • Advisable in the absence of a structural penile abnormality to reduce risk of UTI
  2. Orchidopexy
     • Best accomplished by transperitoneal mobilization before 1 year of age to maintain the germ cell population and protect spermatogenesis.
       • Transabdominal complete mobilization of the spermatic cord almost always allows the testis to be positioned in the dependent portion of the scrotum without dividing the vascular portion of the spermatic cord.
  3. Abdominal wall reconstruction
     • Benefits:
       • Improved bladder emptying
       • Improved defecation
       • More effective cough
       • Psychosocial benefits
  4. Reduction Cystoplasty
     • In many PBS patients, poor bladder contractibility leads to incomplete and infrequent emptying from the complicating urinary stasis and VUR issues. This leads to the concept of reducing the size of the bladder and remodeling it into a more spherical shape to direct better the contractible forces
  5. Upper urinary tract reconstruction
     • Controversial
     • Indications (3):
       1. Declining renal function in the presence of hydronephrosis
       2. Progression of the hydroureteronephrosis
       3. Recurrent upper tract infections
  6. Internal urethrotomy
     • Indicated in the rare patient with true anatomic urethral obstruction or in patients with urodynamic evidence of urethral obstruction by pressure-flow studies.

References

• Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, vol 4, chap 140