Clinical Information

Autosomal dominant polycystic kidney disease (ADPKD) typically manifests in adulthood and is primarily characterized by bilateral kidney cysts, liver cysts, and an increased risk for intracranial aneurysm.(1) Less commonly, symptoms of ADPKD can manifest in childhood or adolescence.(2) Two genes, PKD1 and PKD2, account for the majority of cases of ADPKD, with approximately 78% of cases being attributed to disease-causing variants in the PKD1 gene and approximately 15% of cases being attributed to disease-causing variants in the PKD2 gene.(1) Disease-causing variants in 2 other genes, DNAJB11 and GANAB, are estimated to account for less than 1% of ADPKD cases. The lifetime penetrance of bilateral cysts is close to 100% in individuals with ADPKD, but disease manifestation is typically age-dependent and gene-dependent.(3)

ADPKD can have significant clinical overlap with other autosomal dominant conditions in which bilateral kidney cysts are a common feature, including autosomal dominant tubulointerstitial kidney diseases due to disease-causing variants in the HNF1B or UMOD genes.(1)

Rarer causes of autosomal dominant conditions with overlapping ADPKD features are emerging. The ALG8 gene is most commonly associated with polycystic liver disease, however case reports have identified isolated, bilateral kidney cysts in a small number of individuals.(4) The ALG9 gene is primarily associated with autosomal recessive congenital disorder of glycosylation, type I, but recent studies have identified isolated, bilateral kidney cysts in heterozygous carriers.(5)