ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 51 EN1.1 | DOI: 10.1530/endoabs.51.EN1.1

Skeletal dysplasias-diagnosis, management and prospects for future therapies

Michael Wright


The skeletal dysplasias or genetic skeletal disorders (GSDs) are a heterogeneous group of over 450 conditions associated with varying degrees of disproportionate short stature. The diagnosis of these conditions has relied on a combination of clinical and radiographic assessment. The original classifications of the GSDs was based on x-ray imaging, but Spranger and others predicted that there would be ‘families’ of GSDs with the same underlying molecular basis. The advent of molecular testing for these conditions has confirmed this hypothesis with the delineation of a large number of different spectra of conditions associated with sequence variants in genes e.g. the FGFR3 gene, type II collagen gene and the gene encoding COMP. Conversely this type of analysis has uncovered genetic heterogeneity in what were initially thought to be single phenotypes e.g. multiple epiphyseal dysplasia. Molecular analysis using multigene panels and clinical exomes has, as a result, become more common and in some centres routine. The interpretation of results from these multigene analyses requires great caution to ensure that background genetic variation is not interpreted as pathogenicity. Treatment of patients with GSDs has traditionally been focused on appropriate input from physiotherapists and occupational therapists with orthopaedic, neurosurgical and ENT intervention required in a significant proportion of children and adults. Pharmacotherapies in this group of conditions are best illustrated by the use of bisphosphonates in patients with osteogenesis imperfecta. More recently potential treatments have been developed which target key elements of the molecular pathways involved in the pathogenesis of these conditions. We and others have suggested that it may be possible to repurpose existing therapeutic agents based on improved understanding of molecular pathology of these conditions and recognition of previously unknown effects of existing drugs. We will describe some of our current work in this area.

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