Kidneys

A spectrum of renal abnormalities extends from normal renal parenchyma to dysplasia (Fig. 123–1). The more severely dysplastic kidneys are generally associated with bladder outlet obstruction in which there has not been decompression through a patent urachus (Potter, 1972). Dysplasia is present in 50% of cases; however, it may vary in degree and laterally (Rogers and Ostrow, 1973; Stephens, 1983). Renal dysplasia in PBS of the Potter type II and IV varieties is seen. The Potter type II variety with few nephrons and parenchymal disorganization is more indicative of a renal mesenchymal defect, whereas the Potter type IV with cortical and tubular cysts is associated with outlet obstruction (Wigger and Blanc, 1977).

Figure 123–1 Ultrasound scan of a kidney of a newborn with prune-belly syndrome demonstrating markedly echogenic renal parenchyma and cortical cysts indicative of renal dysplasia.

The renal collecting system is characteristically dilated, often to a severe degree. The degree of dilation, however, does not correlate with the degree of renal dysplasia. Calyceal morphology may be well preserved, even in the presence of massively dilated ureters and renal pelves (Berdon et al, 1977). Ureteropelvic junction obstruction can occur on a primary or secondary basis; however, nonobstructive hydronephrosis is the rule (Woodard and Parrott, 1978b). It is renal infection rather than obstruction that poses the greatest risk to renal function.

Ureters

The ureters are typically dilated, tortuous, and redundant (Fig. 123–2). The proximal (upper) portions of the ureters are usually less abnormal than the distal segments, although massive dilation and stenosis can occur at all levels. Histologic sectioning demonstrates a lack of smooth muscle cells and an increase in fibrous connective tissue. Generally there are more normal-appearing smooth muscle cells in the proximal segments (Palmer and Tesluk, 1974; Stephens, 1983). This fact is critical when ureteral reconstruction is undertaken. The ratio of collagen to smooth muscle cells in prune-belly ureters has been noted to be elevated, especially in refluxing ureters (Gearhart et al, 1995). A decreased number of thick and thin myofibrils noted on ultrastructural examination is thought to contribute to the poor peristalsis (Berdon et al, 1977; Stephens, 1983).

Figure 123–2 Excretory urogram of a patient with prune-belly syndrome; note ureters displaced laterally and calyces relatively well preserved.

Vesicoureteral reflux is present in 75% of children with PBS (Berdon et al, 1977; Fallat et al, 1989) (Fig. 123–3). Obstruction is not common but has been reported at both the ureteropelvic and ureterovesical junctions (Wigger and Blanc, 1977; Moerman et al, 1982; Manivel et al, 1989).

Figure 123–3 Voiding cystourethrogram of a child with prune-belly syndrome demonstrating urethral atresia, urachal diverticulum, and vesicoureteral reflux (VUR).

These large ureters may have ineffective peristalsis because of poor ureteral wall coaptation. The ureteral conduction wave reaches a reduced smooth muscle cell population of poor contractile potential related to reduced myofibrils, often separated by patches of collagen with a resulting bolus of urine reaching more dilated ureteral segments as it progresses toward the bladder (Woodard and Smith, 1998). This can be seen fluoroscopically as ineffective peristalsis, resulting in upper tract stasis, which may lead to infection (Nunn and Stephens, 1961; Williams and Burkholder, 1967).

Bladder

The bladder usually appears massively enlarged with a pseudodiverticulum at the urachus (Fig. 123–4). The urachus is patent at birth in 25% to 30% of children (Lattimer, 1958; Wigger and Blanc, 1977; Stephens and Gupta, 1994). Histologically, the bladder has an increased ratio of collagen to muscle fibers in the absence of obstruction (Workman and Kogan, 1990). The wall is smooth, unlike that seen in obstructed bladders. The pelvic distribution of ganglion cells has been shown to be normal (Nunn and Stephens, 1961; Burke et al, 1969). Smooth muscle hypertrophy is seen, however, in the obstructed prune bladder (Perlmutter, 1976). Stephens demonstrated that the trigone is splayed with the ureteral orifices displaced laterally and superiorly, possibly contributing to the high incidence of reflux (Williams and Burkholder, 1967).

Figure 123–4 Voiding cystourethrogram of a child with prune-belly syndrome demonstrating prostatic urethral enlargement related to a hypoplastic prostate.

On voiding, the bladder neck opens widely into a dilated prostatic urethra (see Fig. 123–4). Urodynamic assessment generally shows normal compliance; however, there is a delayed first sensation to void and large capacity (Snyder et al, 1976). The ability to empty the bladder is variable, with some emptying well and others carrying a significant postvoid residual. This is thought to be due to a relative outlet obstruction and the ability of the bladder to generate sufficient pressure with a detrusor contraction. When the relative outflow resistance prevents effective bladder emptying, the term unbalanced voiding is used (Snyder et al, 1976; Kinahan et al, 1992). Despite these limitations, about 50% of prune-belly patients void spontaneously with normal voiding pressures, normal flow rates, and low postvoid residuals (Nunn and Stephens, 1961; Kinahan et al, 1992). However, as Kinahan and colleagues (1992) demonstrated, deterioration of balanced voiding can occur, resulting in significant postvoid residuals, emphasizing the need for periodic assessment.

Prostate and Accessory Sex Organs

The dilation of the posterior urethra is due to prostatic hypoplasia, probably related to abnormal mesenchymal-epithelial development (Stephens and Gupta, 1994). Histologically, there are few prostatic cellular elements with a reduction of both epithelial and smooth muscle cells and an increase in connective tissue cells (Moerman et al, 1982; Popek et al, 1991; Stephens and Gupta, 1994). Various obstructive lesions of the distal posterior urethra have been described—urethral atresia, valves, urethral stenosis, urethral membrane, and urethral diverticulum—and are thought to occur in 20% of cases (Hoagland and Hutchins, 1987). Stephens (1983) described an angulation of the urethra during voiding, referred to as type IV valves, which results from lack of prostatic parenchymal tissue. Prostatic hypoplasia, the etiology of which is controversial, is thought to be a factor in the ejaculatory failure of PBS patients (Volmar et al, 2001). The vas deferens and seminal vesicles are often atretic, although either may be dilated or thickened (Stephens and Gupta, 1994). The epididymis may be poorly attached to the testis, as is seen commonly in abdominal undescended testes. There may also be lack of continuity between the efferent ductules and the rete testis. Ejaculation is usually in a retrograde fashion because of an incompetent bladder neck.

Anterior Urethra

Although the anterior urethra of the PBS child is usually normal, several anomalies of the anterior urethra have been reported, the most common being urethral atresia and megalourethra (Kroovand et al, 1982; Perrotin et al, 2001). Unless it is associated with a patent urachus, urethral atresia is often lethal (see Fig. 123–3). It has been postulated that urethral atresia or microurethra occurs because the urethra is unused rather than malformed. Spontaneous bladder rupture with fistula formation has also been reported (Reinberg et al, 1993).

PBS is associated with two variations of megalourethra (Shrom et al, 1981; Mortensen et al, 1985). The fusiform type is a deficiency of the corpus cavernosum, as well as the spongiosum, and the scaphoid variety is a deficiency of the spongiosum only with preservation of the glans and corpora cavernosa (Fig. 123–5). With the scaphoid variety, the ventral urethra dilates with voiding, whereas with the fusiform variety the entire phallus dilates with voiding. The fusiform variety is thought to result from a mesenchymal deficiency of the urethral folds, whereas the scaphoid variety results from a mesenchymal deficiency of the urethral supportive tissues (Dorairajan, 1963). Megalourethra is more commonly seen in PBS than any other syndrome (Appel et al, 1986). Transient in utero obstruction of the junction between the glanular and penile urethra has been proposed to cause megalourethra.

Figure 123–5 Scaphoid megalourethra with hypospadiac orifice of prune-belly syndrome.

(Courtesy of C. Peters.)

Testes

Bilateral intra-abdominal testes lying over the iliac vessels are the most typical findings. Although mechanical forces such as a distended bladder and intra-abdominal pressure have been implicated in maldescent of the testes (Kaplan et al, 1986; Hutson and Beasley, 1988), the fact that some patients with the typical urinary tract and abdominal musculature anomalies (termed pseudoprune patients) may have descended testes raises some doubt about pure mechanical factors.

Pak and colleagues (1993) compared the histology of the testes in PBS patients with that of non–prune-belly intra-abdominal testes and that of age-matched control subjects. They found no difference in germ cell counts, Ad spermatogonia, and Leydig cells between PBS testes and non-PBS intra-abdominal testes. However, because germ cell counts in PBS patients younger than 1 year are similar to those of age-matched controls, the implication is that the environmental state of the abdomen is a major factor in their later spermatogenic potential (Nunn and Stephens, 1961; Coplen et al, 1996). This mirrors findings of Nunn and Stephens (1961) of normal germinal epithelium of fetal and newborn PBS testes. Alternatively, Orvis and colleagues (1988) noted decreased numbers of spermatogonia and Leydig cell hyperplasia in fetal PBS testes, implying an intrinsic testicular abnormality. Azoospermia was found in adult PBS patients, and no PBS patient has been reported to have fathered a child (Woodhouse and Snyder, 1985). More recently, Ross and colleagues (1998) have documented paternity in three adults with classic PBS, achieved by sperm retrieval techniques and intracytoplasmic sperm injection. The infertility is thought to be due to a combination of testicular histologic abnormalities, structural defects of the ducts, and prostatic abnormalities (Tayakkanonta, 1963).

Three cases of testis tumor have been reported (Woodhouse and Ransley, 1983; Sayre et al, 1986; Massad et al, 1991; Parra et al, 1991). Massad and colleagues (1991) described histologic testicular patterns similar to those in intratubular germ cell neoplasia in three infants. Although the risk of malignancy may be relatively low considering the lack of germinal epithelium (Uehling et al, 1984), it is clear that placement of the testis in the scrotum and long-term follow-up are necessary to reduce the risk of testicular malignancy and enhance detection.

Abdominal Wall Defect

The appearance of the abdominal wall gives PBS of newborns their most characteristic feature (Fig. 123–6). Although in some cases the musculature of the abdominal wall may be totally absent (Manivel et al, 1989), most commonly there is uneven involvement with the medial and inferior muscular typically most deficient (Mininberg et al, 1973; Randolph, 1977). The appearance at birth is that of wrinkled, redundant skin with an abdomen that bulges in the flanks. One may be able to discern intra-abdominal organs through the thinned abdominal wall. The most severely affected areas may have skin, subcutaneous fat, and a single fibrous layer on the peritoneum (Mininberg et al, 1973; Baird and Sadovnick, 1987). Randolph conducted electromyographic mapping and demonstrated the inferior and medial segments to be most consistently affected (Randolph et al, 1981a). Electron microscopy has demonstrated a nonspecific pattern of myofilament disarray, Z-line disorganization, and mitochondrial proliferation (Afifi et al, 1972; Randolph et al, 1981b; Woodard and Smith, 1998). The fact that normal spinal anterior horn cells have been shown rules out a neuropathic etiology for the muscular deficiency (Nunn and Stephens, 1961). The muscular deficiency, however, is typically inconsistent and patchy.

Figure 123–6 Wrinkled abdomen of a newborn with prune-belly syndrome.

(Courtesy of C. Peters.)

As the child grows older, the abdomen becomes less wrinkled and takes on more of a pot-bellied appearance (Fig. 123–7). Gait is usually not affected, although it may be delayed, and the children tend to roll to their side and use their arms to sit from a supine position. The poor support of the lower chest wall results in flaring of the costal margin (Woodard and Smith, 1998). These children are more vulnerable to respiratory illness because their cough effectiveness is compromised. In spite of these abdominal wall issues, Woodard and Smith (1998) reported good wound healing without a tendency toward infections or incisional hernias.

Figure 123–7 Older child with prune-belly syndrome, showing the absence of wrinkling, the “potbelly” appearance, and the consequent deformity of the lower ribs.

Cardiac Anomalies

Cardiac anomalies such as patent ductus arteriosus, atrial septal defect, ventricular septal defect, and tetralogy of Fallot occur in 10% of children with PBS (Adebonojo, 1973). Cardiac abnormalities at birth may take precedence over urologic issues.

Pulmonary

Pulmonary difficulties can be observed at any age in patients with PBS. Pulmonary hypoplasia can result from severe oligohydramnios related to renal dysplasia or severe bladder outlet obstruction and may result in newborn demise. In addition, pneumothorax and pneumomediastinum can be seen with or without pulmonary hypoplasia (Skoog, 1992). Significant pulmonary difficulties have been reported in 55% of PBS survivors (Geary et al, 1986). The lack of ability to generate significant intra-abdominal pressure may contribute to pneumonia and lobar atelectasis (Alford et al, 1978; Ewig et al, 1996). Acute respiratory illnesses or an anesthetic procedure can easily lead to respiratory insufficiency in the PBS patient, who may have underlying chronic bronchitis from repeated respiratory illnesses. Many patients demonstrate significant restrictive lung disease secondary to musculoskeletal abnormalities such as scoliosis, rib cage abnormalities, and compromised abdominal musculature (Coplen et al, 1996).

Gastrointestinal Abnormalities

In at least 30% of cases, gastrointestinal anomalies are observed. The majority of the anomalies result from incomplete rotation of the midgut giving way to a wide mesentery, which results in increased bowel mobility with intestinal malrotation, volvulus, atresias, and stenosis (Silverman and Huang, 1950; Wright et al, 1986). Splenic torsion related to abnormal mesenteric fixation has also been reported (Heydenrych and Du Toit, 1978; Teramoto et al, 1981). Omphalocele, gastroschisis, and anorectal abnormalities have been reported (Petersen et al, 1972; Morgan et al, 1978; Wilbert et al, 1978; Short et al, 1985; Walker et al, 1987). With a limited ability to generate intra-abdominal pressure, constipation becomes a lifelong problem and leads to acquired megacolon (Woodard and Smith, 1998).

Orthopedic

Orthopedic abnormalities, ranging in incidence from 30% to 45%, are second in frequency to those of the genitourinary tract and abdominal wall. Many of these abnormalities result from the compressive effects of oligohydramnios. Some think the musculoskeletal defects result from the abnormal mesenchymal development at 6 weeks of gestation (Loder et al, 1992). Green and colleagues (1993), however, pointed out that because many of the deformities are unilateral, oligohydramnios is the most likely etiology. Dimpling of the lateral aspect of the knees is a common finding in oligohydramnios. Oligohydramnios may also result in talipes equinovarus (26%), hip dysplasia (5%), and congenital scoliosis (4%) (Woodard and Smith, 1998). It has been proposed that a distended bladder that may impinge on the external iliac vessels may compromise the blood supply to the lower extremities and in severely affected cases result in lower extremity hypoplasia, absence, or amputation (Smith, 1913; Green et al, 1993).