Familial posterior urethral valves as a cause for prune-belly

Abstract

The triad of abdominal muscle deficiency, urinary tract dilation, and cryptorchidism defines prune-belly (PB). The etiology is unknown and undoubtedly heterogeneous. Severe obstructive uropathy (OU) has been suggested as the common factor leading to PB. Posterior urethral valves (PUV) are the most common cause of OU in males, but do not occur in females. The precise embryonic origin of PUV is not known, but may be remnants of the urogenital membrane, residual mesonephric tissues, or exaggerated expression of normal structures. PUV are usually sporadic with rare familial recurrence. Transcription controlling genes such as the HOX genes have been cited as potentially contributing to PB in at least some cases. Some of the HOX genes are known to be important in urogenital morphogenesis. We have recently encountered a family with 3 males in 2 generations with PUV and PB. Oligohydramnios was diagnosed in the proband at 20 weeks gestation by ultrasonography. Additional findings included a massively distended bladder and bilateral clubfeet. Chromosome studies were normal, 46,XY. Autopsy revealed PUV, absence of the abdominal musculature, severe hydronephrosis, and pulmonary hypoplasia. Family history was significant for a stillborn maternal uncle with PUV and PB. and a maternal first cousin age 3 years who has PB and renal insufficiency secondary to PUV. To our knowledge, this is the first report of familial PB affecting individuals in 2 generations. However, if one includes milder manifestations of OU without PB at least 2 families with an affected father and son have been reported, suggesting possible autosomal dominant inheritance in at least some families. We found no reports of multi-generational X-linked recessive inheritance of OU or PB; however, several cases of familial recurrence involving siblings or cousins have been reported. The recurrence of PB in this family may represent autosomal dominant inheritance with sex-limited expression or X-linked inheritance of PUV. Future studies involving families such as this will allow identification of the genetic causes of PUV and related disorders.