Human renal adysplasia usually occurs sporadically, and bilateral disease is the most common cause of childhood end-stage renal failure, a condition that is lethal without intervention using dialysis or transplantation. De novo heterozygous mutations in Uroplakin IIIa (UPIIIa) are reported in four of 17 children with kidney failure caused by renal adysplasia in the absence of an overt urinary tract obstruction. One girl and one boy in unrelated kindreds had a missense mutation at a CpG dinucleotide in the cytoplasmic domain of UPIIIa (Pro273Leu), both of whom had severe vesicoureteric reflux, and the girl had persistent cloaca; two other patients had de novo mutations in the 3 UTR (963 T3 G; 1003 T3 C), and they had renal adysplasia in the absence of any other anomaly. The mutations were absent in all sets of parents and in siblings, none of whom had radiologic evidence of renal adysplasia, and mutations were absent in two panels of 192 ethnically matched control chromosomes. UPIIIa was expressed in nascent urothelia in ureter and renal pelvis of human embryos, and it is suggested that perturbed urothelial differentiation may generate human kidney malformations, perhaps by altering differentiation of adjacent smooth muscle cells such that the metanephros is exposed to a functional obstruction of urine flow. With advances in renal replacement therapy, children with renal failure, who would otherwise have died, are surviving to adulthood. Therefore, although the mechanisms of action of the UPIIIa mutations have yet to be determined, these findings have important implications regarding genetic counseling of affected individuals who reach reproductive age.

These disappointing results, even in the hands of specialists, highlight the importance of late followup and challenge the prevailing assumption that total correction can be achieved with a single stage operation in infancy. Although simple exteriorization of a low vagina can reasonably be combined with cosmetic correction of virilized external genitalia in infancy, we now believe that in some cases it may be best to defer definitive reconstruction of the intermediate or high vagina until after puberty. The psychological issues surrounding sexuality in these patients are inadequately researched and poorly understood.

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Objective To compare the diagnostic accuracy of twodimensional (2D) ultrasound and three-dimensional (3D) computed tomography (CT) for the diagnosis of fetal skeletal anomalies. Methods