PRUNE BELLY SYNDROME
The prune belly syndrome (PBS, also known as Eagle-Barrett or triad syndrome) is a rare, congenital disorder that occurs almost exclusively in males. Its major features include deﬁcient abdominal wall musculature, bilateral cryptorchidism, and urinary tract anomalies that include renal dysplasia, hydronephrosis, and dilation of the ureters and bladder.
PBS occurs in approximately 3.5 per 100,000 live male births. Blacks are at increased risk and Hispanics are at decreased risk when compared with the overall population. There are rare reports of females born with deﬁcient abdominal wall musculature and urinary tract anomalies, although their ovaries are generally normal.
Appearance of abdominal wall in prune belly syndrome
The pathogenesis of PBS remains poorly understood. One theory argues that early obstruction of the bladder outlet causes dilation of the bladder, ureters, and then renal pelves. Such dilation is posited to cause an increase in intraabdominal pressure that results in atrophy of the abdominal wall musculature and inhibition of normal testicular descent. This hypothesis, however, is challenged by the fact that many patients with PBS do not have an anatomic outlet obstruction, and that many patients who do have such obstructions (such as those with posterior urethral valves) do not have PBS.
Another theory argues that the primary defect lies in the intermediate and lateral plate mesoderm, which gives rise to the urinary tract, genital tract, and abdominal wall musculature (see Plate 2-1). The causes and nature of the mesodermal defect, however, remain unknown. Because 1 in 23 children with prune belly syndrome is the product of a twin pregnancy, however, at least some cases could reﬂect an uneven distribution of mesoderm between twinned embryos early in gestation.
The genetics of PBS also remain poorly understood. Although most cases are sporadic, a small number of familial cases have been reported and suggest a sex-linked autosomal recessive pattern of inheritance. Most affected infants possess normal karyotypes, but some associations have been noted with trisomies 13, 18, and 21.
Presentation And Diagnosis
PBS can often be detected using prenatal ultrasound, which has been shown to establish the diagnosis as early as 11 weeks into gestation. Suggestive ﬁndings include hydronephrosis, bladder enlargement, and absence of the abdominal musculature. If there is severe renal dysplasia or a bladder outlet obstruction, oligohydramnios and pulmonary hypoplasia may also be seen.
If PBS is not diagnosed in the antenatal period, it is generally readily apparent at birth. The most striking feature of affected infants is the wrinkled, prunelike skin overlying their inferior abdominal wall, which reﬂects attenuation or outright absence of the normal abdominal musculature. The abdominal wall may be so thin that the underlying organs, including peristaltic regions of the bowel, become visible. As affected children grow older and spend more time standing upright, the wrinkles become less prominent, and the abdomen assumes a “pot-bellied” appearance. The lack of abdominal musculature makes it difﬁcult for affected patients to sit upright from a supine position. Some reports have also suggested that it increases the risk of pneumonia by impairing the normal coughing mechanism, and that it can cause constipation by preventing the generation of increased intraabdominal pressure.
Although all patients have hydronephrosis, the degree of renal dysplasia is variable and has important prognostic implications. Those with the most severe renal dysplasia develop the Potter sequence (Plate 2-8) and typically succumb to severe respiratory distress shortly after birth. Those with moderate dysplasia often develop end-stage renal disease (ESRD) during childhood. Finally, those with minimal or no dysplasia often maintain normal or near-normal renal function. To assess for renal abnormalities, an ultrasound should be performed in the neonatal period, and serial measurements of the serum creatinine concentration should be obtained (recognizing that early values reﬂect maternal, rather than neonatal, renal function). If there is evidence of renal dysfunction, a renal scan can provide more detailed functional information.
The ureters appear broad and tortuous, especially as they approach the bladder, and peristalsis is weak and ineffective. These anomalies reﬂect a relative lack of smooth muscle cells in the ureteral walls, which instead consist primarily of ﬁbrous connective tissue. In addition, the ureteric oriﬁces are often at abnormally lateral positions, which predisposes them to reﬂux.
The bladder appears enlarged, with a vesicourachal diverticulum often present. The bladder wall appears smooth and thick secondary to increased collagen depo- sition. The detrusor muscle is hypoplastic, which may cause weak bladder contractions associated with large postvoid residuals. The combination of urinary stasis in the bladder, which increases the risk of bacterial infection, and vesicoureteral reﬂux, which permits passage of infected urine into the renal pelves, may lead to recurrent pyelonephritis and progressive worsening of renal function. Thus if there is evidence of bladder dysfunction, a VCUG should be performed after sufﬁcient antibiotic prophylaxis has been provided.
The bladder neck and prostatic urethra appear widened, with the latter resulting from prostatic hypoplasia. The prostatic urethra tapers to the membranous urethra, resulting in an inverted triangle appearance on VCUG. The anterior urethra is typically normal. A small subset of patients may have urethral dilation (megalourethra) owing to absence of either the corpora spongiosum alone or, in rare cases, both the corpora spongiosum and cavernosum. An even smaller number of patients have complete urethral atresia, resulting in oligohydramnios and Potter sequence.
The testes are generally located in the abdomen, near or above the iliac vessels. They appear histologically abnormal, with a reduced number of spermatogonia, and are at increased risk for malignancy. The combination of testicular dysfunction and prostatic hypoplasia renders patients infertile. In addition, retrograde ejaculation is common because of the open bladder neck.
Other organ systems show a variable degree of involvement. Cardiac anomalies, seen in 10% to 20% of patients, include septal defects and patent ductus arteriosus. Pulmonary anomalies include pulmonary hypoplasia, which occurs in those with Potter sequence, as well as pneumothorax. Early assessment for cardiopulmonary anomalies, including a chest radiograph, is thus an important component of the postnatal evaluation. Finally, gastrointestinal complications range from constipation, which occurs in most patients, to serious anomalies such as intestinal malrotation or anorectal malformations.
Appearance of kidneys, ureters, and bladder in prune belly syndrome
Because recurrent pyelonephritis is common and can lead to renal scarring, lifelong antibiotic prophylaxis should be started during the postnatal period. In addition, urine cultures and measurements of the serum creatinine concentration should be obtained on a regular basis.
If bacterial infections continue to occur, or if renal function appears to be deteriorating, the abnormal collecting system may be reconstructed. The ureters are tapered and reimplanted to reduce reﬂux. In addition, a reduction cystoplasty, which consists of excision of the vesicourachal diverticulum or other redundant areas of mucosa, may be performed to reduce the volume of retained urine. Although the majority of patients empty their bladders adequately, a subset require clean intermittent catheterization.
Abdominal wall reconstruction can mitigate the psychological effects of PBS, and it may also improve constipation and reduce the risk of pneumonia. The most popular technique, known as the Monfort procedure, consists of an elliptical incision to remove redundant skin, a second incision around the umbilicus so that it can remain in position, and two vertical incisions through the abdominal fascia to overlap redundant segments and increase the strength of the abdominal wall. Finally, early orchidopexy is recommended in all patients because it often allows them to achieve normal production of sex hormones at puberty. In addition, it greatly facilitates a regular examination for testicular malignancies.
The prognosis of patients with PBS who survive the postnatal period depends primarily on the severity and progression of renal dysfunction. Unfortunately, even those who survive infancy with mild renal impairment may progress to renal failure due to recurrent pyelonephritis, particularly in patients who incompletely empty their bladders. Renal transplantation has been shown to be a feasible option for these patients.