Genetic and Clinical Evaluation of Pediatric Cystic Kidney Diseases: Autosomal Dominant and Autosomal Recessive Polycystic Kidney Disease

Abstract

Cystic kidney diseases are an important cause of pediatric morbidity and mortality. Most genetic cystic kidney diseases are “ciliopathies”, a group of disorders that share a common feature of abnormal structure or function of the primary cilia. Ciliopathies represent a broad range of clinically and genetically heterogenous disorders, which affect multiple organ systems. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the 2 most common etiologies, affecting 1:1000-2500 and 1:20,000-40,000 individuals, respectively. Although historically referred to as “adult” (ADPKD) and “infantile” (ARPKD) polycystic kidney disease, it is now understood that age at presentation is variable. Approximately 3% of ADPKD patients present with very early onset, severe features that mimic (“phenocopy”) typical ARPKD. Similarly, a minority of ARPKD cases present as late as young adulthood. Due to their heterogeneity, ADPKD, ARPKD, and other phenocopies, such as hepatocyte nuclear factor-1 beta-associated kidney disease, can be difficult to distinguish clinically, making molecular genetic testing a valuable diagnostic resource. The purpose of this review is to provide a comprehensive overview of the clinical and genetic spectrum and molecular diagnosis of cystic kidney diseases in children, with a specific focus on ADPKD and ARPKD.