<unk>  is genetically heterogeneous with two genes identified:<unk>  (chromosome region 16p13.3; around 85% cases) and PKD2 (4q21; around 15% cases). Several genetic mechanisms probably contribute to the phenotypic expression of the<unk> . Although evidence exists for a two-hit mechanism (germline and somatic inactivation of two PKD alleles) explaining the focal development of renal and hepatic cysts, haploinsufficiency is more likely to account for the vascular manifestations of the<unk> . Additionally, new mouse models homozygous for<unk>  hypomorphic alleles 22 and 23 and the demonstration of increased renal epithelial cell proliferation in PKD2 +/− mice suggest that mechanisms other than the two-hit hypothesis also contribute to the cystic phenotype. Large interfamilial and intrafamilial variability occurs in<unk> . Most individuals with<unk>  mutations have kidney failure by age 70 years, whereas more than 50% of individuals with PKD2 mutations have adequate renal function at that age (mean age of onset of end-stage renal<unk> : 54·3 years with<unk> ; 74·0 years with PKD2). The significant intrafamilial variability observed in the severity of renal and extrarenal manifestations points to genetic and environmental modifying factors that may influence the outcome of<unk> , and results of an analysis of the variability in renal function between monozygotic twins and siblings support the role of genetic modifiers in this<unk> . It is estimated that 43–78% of the variance in age to ESRD could be due to heritable modifying factors, with parents as likely as children to show more severe<unk>  in studies of parent-child pairs.
Autosomal dominant polycystic kidney disease
Autosomal recessive polycystic kidney disease
Medullary cystic kidney disease
Glomerulocystic kidney disease
Medullary sponge kidney
Juvenile nephronophthisis
Horseshoe kidney
Multicystic dysplastic kidney