Prune belly syndrome (ORPHA:2970)
A rare lower urinary tract obstruction (LUTO) characterized by varying degrees of an enlarged urinary bladder, dilated ureters, hydronephrosis, and poorly contractile and disorganized detrusor and ureteral smooth muscle, in association with hypoplastic or absent midline abdominal skeletal musculature, and bilaterally undescended testes in males.
Epidemiology
Data on prevalence is limited. Birth prevalence is estimated in Canada and the United states at 1/29,000 and 1/26,500, respectively; 95% of cases occur in males.
Clinical description
The spectrum ranges from mildly affected individuals to lethality. Prune belly syndrome (PBS) often presents antenatally on routine ultrasound with oligohydramnios and a very large, distended bladder, mild to severe bilateral hydroureteronephrosis, fetal ascites and, occasionally, renal dysplasia and a patent urachus. Other anomalies include cryptorchidism, pulmonary hypoplasia, club foot and features of Potter sequence. The syndrome is associated with pulmonary, skeletal, cardiac, and gastrointestinal defects and may be associated with atresia of the urethra. Newborns present with a wrinkled abdomen that later develops a 'pot belly' appearance. There is a predisposition to urinary tract infections due to incomplete bladder emptying in children.
Etiology
Whilst the exact mechanism is still unknown, pathogenesis is mainly related to urethral obstruction or mesodermal developmental defect. Urethral obstruction early in development causes massive bladder distention and urinary ascites that leads to underdevelopment of the abdominal wall musculature and failure of testicular descent. The impaired elimination of urine from the bladder leads to oligohydramnios and, depending on severity, lung hypoplasia and Potter sequence, as well as a profound and lifelong effect on kidney, ureteral and bladder function. Whilst most cases are sporadic, a few cases of siblings have been linked to mutations in CHRM3 (1q43). Several candidate genes have been suggested, but there is limited evidence to support them as a monogenic cause. Copy number variations may cause unexplained genetic cases of PBS.
Diagnostic methods
Diagnosis is usually antenatal. Postnatal diagnosis is based on characteristic clinical findings, assessment of pulmonary function, renal function, ultrasound and voiding cystourethrogram.
Differential diagnosis
Differential diagnoses in utero include megacystis/megaureter, megacystis microcolon intestinal hypoperistalsis syndrome or posterior urethral valves. PBS has also been reported in trisomy 13, 18, 21 and large chromosome 6 deletions.
Antenatal diagnosis
Antenatal diagnosis is based on ultrasound findings. As with all forms of LUTO, counseling should include the spectrum of postatal manifestations.
Genetic counseling
The majority of the cases are sporadic. Autosomal recessive inheritance is reported for CHRM3. Autosomal dominant and X linked inheritance havs been suggested in other familial cases.
Management and treatment
Sonographic monitoring of the urinary tract and amniotic fluid volume is required throughout pregnancy. Early decompression of severe bladder outlet obstruction that contributes to oligohydramnios is advised. Antibiotic prophylaxis is started at birth. Where possible patients are managed conservatively. Indication for early surgery is only mandatory when urethral atresia is present, and when there is a decline in renal function or failure to prevent or eradicate infection using conservative measures . Further treatment may include bilateral orchidopexies, abdominoplasty in addition to potential urologic reconstructive surgery. Transplantation is indicated for renal failure.
Prognosis
The postnatal course of PBS infants is dictated by renal function and by their co-morbidities, and the risk is stratified accordingly. 20% of patients are at a high risk of severe renal dysfunction and pulmonary hypoplasia; another 40% patients have the classic features of PBS with prognosis related to the degree of renal dysplasia, and for who there is a 4% risk of acute renal failure. 40% of patients are low risk with normal renal function and mild phenotypic features of PBS. Prematurity is common and engenders cardiovascular and pulmonary problems. Perinatal mortality rates for PBS are quoted between 10 and 25%.

                            Last update: 
                            November 2020


                            - Expert reviewer(s): 
                            Dr Giovanni MOSIELLO | EUROGEN*


                                * European Reference Network