Abstract
Ciliary chondrodysplasias represent a heterogenous group of rare, nearly exclusively
autosomal recessively inherited developmental conditions. While the skeletal phenotype,
mainly affecting limbs, ribs and sometimes the craniofacial skeleton, is predominant,
extraskeletal disease affecting the kidneys, liver, heart, eyes and other organs and
tissues is observed inconsistently. Significant lethality, resulting from cardiorespiratory
failure due to thoracic constriction as well as from renal and hepatic insufficiency
or primary cardiac failure due to congenital heart disease, is observed with these
conditions. The underlying genetic defects as well as developmental biology and cell
biology work undertaken using animal model systems, suggest that these rare conditions
result from ciliary malfunction. The skeletal phenotype is believed to result from
imbalances in the hedgehog signaling pathway that normally occurs in functional cilia
in chondrocytes. Although phenotypes have been historically distinguished based on
clinical features into short-rib polydactyly syndrome, Jeune asphyxiating thoracic
dystrophy, Mainzer-Saldino syndrome, Sensenbrenner syndrome (cranioectodermal dysplasia),
oral-facial-digital syndrome and Ellis-van Creveld syndrome, recent research suggests
that there is significant genetic as well as phenotypic overlap between the conditions.
This review discusses ciliary chondrodysplasias from phenotypic hallmarks to clinical
management and summarizes progress in identification of the underlying molecular mechanisms
as well as potential future therapeutic perspectives.
Keywords
Cilia - chondrodysplasia - Jeune syndrome - short-rib polydactyly syndrome - Sensenbrenner
syndrome
