Prune belly syndrome

Prune-belly syndrome is a rare congenital condition that predominantly affects males and is defined by a clinical triad: deficiency of the anterior abdominal-wall skeletal musculature resulting in a characteristic wrinkled, ‘prune-like’ abdomen, urinary tract distension (including megacystis, hydroureter, and hydronephrosis) due to smooth muscle dysfunction, and bilateral intra-abdominal testes. The condition is congenital and is commonly detected prenatally by ultrasonography demonstrating megacystis combined with abdominal-wall laxity. Additional features may involve the pulmonary system (hypoplasia secondary to oligohydramnios in severe cases), the gastrointestinal tract (constipation, malrotation, intestinal hypoperistalsis in overlap forms), and the musculoskeletal system (talipes equinovarus, hip dysplasia). The clinical spectrum is highly variable, ranging from perinatally lethal forms with severe pulmonary hypoplasia and renal dysplasia to milder presentations compatible with survival into adulthood.

The estimated incidence is approximately 3.8 per 100,000 live male births and 1.1 per 100,000 live female births.

Most cases of prune-belly syndrome are sporadic; rare familial forms with identified Mendelian causes involve variants in genes related to the smooth-muscle contractile apparatus and mechanosensation. Reported genes include CHRM3 (cholinergic signalling, recessive familial form), MYOCD (congenital megabladder/prune-belly sequence), PIEZO1 (compound heterozygous loss-of-function), ACTG2 (smooth-muscle dysfunction with neonatal megacystis), and ACTA2 (multisystem smooth-muscle dysfunction syndrome). The underlying mechanism involves defective development or function of urinary-tract and abdominal-wall smooth muscle together with ventral-body-wall mesoderm, producing the combination of abdominal-wall deficiency, dilated non-obstructed urinary tract, and bilateral cryptorchidism.

Prune-belly syndrome is genetically heterogeneous; most cases are sporadic, while rare familial forms follow an autosomal recessive pattern. Recurrence risk for parents of a sporadic affected child is generally low but is not zero, and counselling should account for the possibility of an unrecognised familial form. Prenatal molecular testing is technically possible once a familial pathogenic variant has been identified.

The clinical diagnosis is established by the characteristic triad on physical examination: the wrinkled “prune-like” abdomen reflecting deficient anterior abdominal-wall musculature, urinary-tract abnormalities, and bilateral cryptorchidism in males. Prenatal ultrasonography typically demonstrates megacystis with hydroureter and hydronephrosis in the presence of abdominal-wall thinning. Postnatal assessment includes renal ultrasound and voiding cystourethrography to characterise the urinary-tract phenotype.

Main differential diagnoses include:

• : megacystis with microcolon and intestinal dysmotility distinguishes MMIHS from prune-belly syndrome (absence of microcolon in the latter)
• (Ochoa syndrome): non-neurogenic neurogenic bladder with characteristic inverted facial expression on smiling or crying; abdominal-wall musculature preserved
• Congenital lower urinary tract obstruction / posterior urethral valves: mechanical urethral obstruction with secondary bladder hypertrophy and upper-tract dilatation; abdominal-wall musculature preserved; usually sporadic

• Molecular genetic testing can establish the underlying genetic cause and confirm the clinical diagnosis at the molecular level.
• A molecular diagnosis helps guide individualised clinical management and supportive care, established by the care team in consultation with the patient and their family.
• Once a familial pathogenic variant has been identified, testing of at-risk family members is technically possible and may clarify their genetic status.

• Conegundes AF, Garcia ISB, Miranda BCB, Borges ARS, Sanglard AD, Ferreira GBM, et al. Prune-belly syndrome: an update. Curr Pediatr Rev. 2025;21(4):304-14. doi:10.2174/0115733963285237240524042142. PMID:.
• Gyawali S, Gyawali B, Ghimire B, Shrestha B, Khanal P, Dahal GR, et al. Prune belly syndrome: a rare case report. Clin Case Rep. 2024;12(6):e8922. doi:10.1002/ccr3.8922. PMID:; PMCID:PMC11183155.
• Amado NG, Nosyreva ED, Thompson D, Egeland TJ, Ogujiofor OW, Yang M, et al. PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder prune belly syndrome. Nat Commun. 2024;15(1):339. doi:10.1038/s41467-023-44594-0. PMID:; PMCID:PMC10771463.