Renal cystic diseases and ciliopathies

Inherited renal cystic diseases comprise a spectrum of disorders that are typically characterized by dysfunction of the so-called cilia. These hair-like cellular appendages are involved in numerous cellular signalling processes. During development, cilia are important for the development of the left–right axis and for the establishment of cell polarity. Consequently, depending on the specific nature of the underlying ciliary defect, renal cystic diseases can be associated with a large spectrum of other organ manifestations, including congenital heart disease, retinopathy, polydactyly, and hepatic abnormalities, such as ductal plate malformation. Based on clustering of such symptoms, specific clinical syndromes, such as nephronophthisis, Bardet–Biedl syndrome, Joubert syndrome, and the various forms of polycystic kidney diseases, have been assigned. Subsequent genetic investigations have shown that these clinical distinctions are not necessarily consistent with the underlying genetic alterations, so that, for example, genes initially associated with Joubert syndrome can phenocopy autosomal recessive polycystic kidney disease. Thus, identification of the genetic cause can inform the clinical management to assess for potentially involved organ manifestations.