Ciliopathy

Cilia arise from basal bodies, which are formed from centrioles, complex microtubule-based structures located within the cytoplasm. Ciliopathies comprise a group of disorders associated with mutations in genes encoding proteins related to formation or function of cilia. As cilia are a component of almost all vertebrate cells, cilia dysfunction can manifest as a constellation of features that include characteristically, retinal degeneration, renal disease and cerebral anomalies. Diverse developmental and degenerative single-gene disorders such as polycystic kidney disease(PKD), nephronophthisis, the Bardet-Biedl syndrome, the Joubert syndrome, and the Meckel syndrome are categorized as ciliopathies.<br>The PKD are transmitted as autosomal-dominant(ADPKD)or autosomal-recessive(ARPKD)traits. Although both forms of PKD initiate early in life, ARPKD rapidly progresses to kidney failure shortly after birth whereas ADPKD can take many years to reach end-stage renal disease(ESRD). Although both forms of the disease are characterized by the development and expansion of numerous fluid-filled cysts in the kidney as well as defects in multiple other tissues, the distribution of the renal cysts and the other body organs affected vary. Significantly, ADPKD is one of the most common human monogenic diseases with an incidence of 1:200–1,000; it is a systemic disorder, characterized by fluid-filled cysts not only in the kidneys but also in liver, pancreas, and other organs as well as cardiovascular defects and aneurysm. Although the incidence of ARPKD is lower at 1:10,000–40,000 it is associated with a high level of mortality in affected newborns. Most cases manifest in utero or at birth with renal enlargement and biliary dysgenesis. In ADPKD the causative genes are PKD1 and PKD2 that encode polycystin-1 and polycystin-2, respectively, whereas mutations in a single gene, PKHD1, cause ARPKD.<br>Nephronophthisis is the most common genetic cause of chronic kidney disease within the first three decades of life. Patients usually present with symptoms of polyuria and polydipsia, secondary enuresis and anemia. Presentation may occur during infancy, but more typically in late childhood with progressive renal failure manifesting during early puberty. Ultrasound features demonstrate normal sized kidneys with loss of cortico-medullary differentiation and increased echogenicity. Histologically, nephronophthisis kidneys are characterised by the presence of cortico-medullary cysts, tubular basement membrane disruption and tubulointerstitial nephropathy. Extra-renal involvement has been described in over 10% of cases and primarily involves retinal disease, fibrocystic liver disease, cerebellar vermis hypoplasia and skeletal dysplasia.