Osteoarthritis as the Presenting Pathology in Patients with Skeletal Dysplasias

Review Article


Peter Kannu ^{1 2 3}, Ravi Savarirayan ^{2 3} and F John Bateman ³
Affiliations: ¹Division of Medical Genetics, Department of Paediatrics, Queen’s University, Kingston, Canada; ²Department of Paediatrics, University of Melbourne, Parkville, Melbourne, Australia and ³Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Australia


ABSTRACT

The understanding of common diseases and disease mechanisms is facilitated by the study of rare disorders, in which mutations associated with a significant functional effect cause an observable phenotype. The challenge clinicians currently face is with regard to patients who are increasingly aware of the importance of genes in common disease development, and expect their physician to clarify their individual disease risks using a genetic model. This review focuses on a subset of genes that have been shown to be responsible for a range of inherited bone and cartilage disorders (chondrodysplasias), which present clinically with disproportionate short stature and/or orthopedic deformity, with the aim of illustrating the growing evidence that mutations/polymorphisms of lesser effect in these genes might predispose to osteoarthritic phenotypes in the general population. The discussion is structured to review chondrodysplasias arising from mutations in different parts of the cellular and extracellular pathways. If we are able to identify robust genetic “profiles” of individuals who are at greater risk of osteoarthritis, this might then enable preventative strategies to be tailored to these groups, as well as enhancing our understanding of this complex disease phenotype.

Keywords: complex disease, osteoarthritis, transcription factors, cell signaling, matrix enzymes, cilia, matrix proteins
Correspondence: Peter Kannu, Queen’s University, Division of Medical Genetics, Kingston K7L3J6, Canada. e‐mail: kannu@queensu.ca