The genetics of urinary tract malformations

In this discussion I have excluded consideration of the genetics of purely renal malformations, such as polycystic kidneys, and of functional disorders of the kidney. Systematic family studies are available for renal agenesis, duplication of the ureters, vesico-ureteric reflux (each probably due to maldevelopment of the ureteric bud), bladder exstrophy and hypospadias as isolated malformations. Renal agenesis has a birth frequency of about 1.2 in 10 000 and the proportion affected of sibs is about 3 per cent. Duplication of the ureter has a birth frequency of about 1 per cent and the proportion affected of sibs and parents of probands is about 12 per cent. Vesico-ureteral reflux also has a prevalence in early childhood of about 1 per cent and the proportion of sibs affected is about 10 per cent. Bladder exstrophy has a birth frequency of about 1 in 20 000 and perhaps about 1 per cent of sibs are affected. Hypospadias has a birth frequency in boys of about 1 in 300 and the proportion affected of brothers is about 10 per cent. Further family studies are needed of these malformations when they occur in isolation. Either the multifactorial threshold model or dominant inheritance with reduced penetrance and varied expressivity would fit the data available.