ABSTRACT
Cilia and ciliary proteins play a crucial role in development and the dysfunction of cilia and ciliary proteins often results in complex syndromal disorders. One site of frequent manifestation of ciliary disorders is the skeleton and the resulting ciliary chondrodysplasias represent a heterogeneous group of rare, nearly exclusivelyautosomal recessive inherited conditions. Frequent manifestations include shortened limbs and ribs, polydactyly as well as craniofacial abnormalities. In addition, extraskeletal disease affecting the kidneys, liver, heart, eyes and other organs and tissues is observed inconsistently. Nevertheless, perinatal and childhood lethality due to cardiorespiratory failure resulting from congenital heart disease and/or thoracic constriction as well as from renal and hepatic insufficiency is significantly observed. Brain malformation, developmental delay and loss of eyesight are additional disabling phenotypes observed. While the exact pathomechanism in these disorders remains to be understood, the skeletal phenotype has been largely attributed to imbalances in the hedgehog signalling pathway, for which chondrocyte cilia play a crucial role. Although phenotypes have been historically distinguished based on clinical features into short rib-polydactyly syndrome (SRPS), Jeune Asphyxiating Thoracic Dystrophy (JATD), Mainzer-Saldino Syndrome (MZDS), Sensenbrenner Syndrome (cranioectodermal dysplasia, CED), Oral-Facial-Digital syndrome (OFD), Axial Spondylometaphyseal Dysplasia (axial SMD) and Ellis-van Creveld syndrome (EVC), recent research suggests that there is significant genetic as well as phenotypic overlap between the conditions. This chapter summarizes phenotypic hallmarks as well as the molecular basis of ciliary chondrodysplasias and gives a short outlook towards clinical management and potential therapeutic approaches.
