Clinical Utility

Polycystic kidney disease (PKD) encompasses both autosomal dominant (ADPKD) and autosomal recessive (ARPKD) forms. ADPKD is characterized by bilateral kidney cysts with extrarenal manifestations including liver cysts, intracranial aneurysms, and cardiac valve abnormalities. Nearly half of individuals with ADPKD develop end-stage kidney disease by age 60. ADPKD typically presents in adulthood, though rare early-onset cases can occur prenatally or in early childhood, mimicking ARPKD (https://search.clinicalgenome.org/kb/genes/HGNC:9008). ADPKD affects approximately 1 in 1,000 individuals, making it one of the most common inherited kidney disorders. ARPKD presents earlier, often prenatally or in infancy, with enlarged kidneys, collecting duct cysts, and congenital hepatic fibrosis. Approximately one-third of ARPKD cases are neonatal lethal.

ADPKD is predominantly caused by pathogenic variants in PKD1 and PKD2, with newly identified genes IFT140, GANAB, and DNAJB11accounting for a small proportion of cases. ARPKD is primarily caused by pathogenic variants in PKHD1, with DZIP1L explaining a minor fraction of cases. Both sequence variants and copy number variants can be causative, though large deletions/duplications are relatively rare. De novo variants occur in approximately 10%-20%of ADPKD cases. The diagnostic yield of this panel will vary based on the clinical phenotype of the patient and it has been reported to be up to approximately 90%. This panel also includes the newly emerged genes although the current evidence is limited to support a causal role such as ALG8 and CYS1.