Educational paper: ciliopathies

Abstract

Cilia are antenna-like organelles found on the surface of most cells. They transduce molecular signals and facilitate interactions between cells and their environment. Ciliary dysfunction has been shown to underlie a broad range of overlapping, clinically and genetically heterogeneous phenotypes, collectively termed ciliopathies. Literally, all organs can be affected. Frequent cilia-related manifestations are (poly)cystic kidney disease, retinal degeneration, situs inversus, cardiac defects, polydactyly, other skeletal abnormalities, and defects of the central and peripheral nervous system, occurring either isolated or as part of syndromes. Characterization of ciliopathies and the decisive role of primary cilia in signal transduction and cell division provides novel insights into tumorigenesis, mental retardation, and other common causes of morbidity and mortality, including diabetes mellitus and obesity. New technologies ("Next generation sequencing/NGS") have considerably improved genetic research and diagnostics by allowing simultaneous investigation of all disease genes at reduced costs and lower turn-around times. This is undoubtedly a result of the dynamic development in the field of human genetics and deserves increased attention in genetic counselling and the management of affected families.

Fig. 1

Schematic diagram of a primary cilium and associated processes. The inner ciliary structure is defined by the axoneme composed of nine microtubule doublets derived from the basal body and mother centriole of the centrosome (inset displays cross-section revealing 9+0 architecture). Along this microtubule core, the transport of proteins toward the tip of the cilium (anterograde, by kinesin-2 with its major component KIF3A) and in the retrograde direction towards the cell body (by dynein-2) is organized by an elaborate process called intraflagellar transport (IFT). Cilia are small antennae that detect a variety of different extracellular stimuli and orchestrate multiple signaling pathways with nuclear trafficking of some molecules

Fig. 2

Enlarged kidney from a patient with autosomal dominant polycystic kidney disease (ADPKD). Multiple cysts, grossly varying in size, have massively destructed the renal parenchyma

Fig. 3

Baby with autosomal recessive polycystic kidney disease (ARPKD). a Distended abdomen due to voluminous kidneys that lead to respiratory problems. b Nephrectomized kidney of this girl. c–d Ultrasound showed symmetrically enlarged echogenic kidneys with fusiform dilations of collecting ducts and distal tubules arranged radially throughout the renal parenchyma from medulla to cortex

Fig. 4

Axial (a) and sagittal (b) MRI of a patient with Joubert syndrome demonstrating the complex mid-hindbrain malformation typical for JSRD with molar tooth sign (MTS) (a) and cerebellar vermis hypoplasia (b)

Fig. 5

Fetus with Meckel syndrome. a Phenotype with occipital meningoencephalocele and a massively malformed brain resembling anencephaly. b Postaxial hexadactyly. c Bilateral considerably enlarged kidneys interspersed with small, pinhead-sized cysts. d Cystic kidney with considerable interstitial fibrosis. e Ductal plate malformation characterized by dysgenesis of the hepatic portal triad with hyperplastic biliary ducts and congenital hepatic fibrosis

Fig. 6

Two brothers affected with Bardet–Biedl syndrome