SHOX deficiency is the most frequent genetic growth disorder associated with isolated and syndromic forms of short stature. Caused by mutations in the homeobox gene SHOX, its varied clinical manifestations include isolated short stature, Léri-Weill dyschondrosteosis, and Langer mesomelic dysplasia. In addition, SHOX deficiency contributes to the skeletal features in Turner syndrome. Causative SHOX mutations have allowed downstream pathology to be linked to defined molecular lesions. Expression levels of SHOX are tightly regulated, and almost half of pathogenic mutations have affected enhancers. Clinical severity of SHOX deficiency varies between genders and ranges from normal stature to profound mesomelic skeletal dysplasia. Zebrafish and chicken animal models together with micromass cultures and primary cell lines have been used to address SHOX function. Pathway and network analysis have identified interacting molecules, target genes, and regulators. SHOX is one of several critical factors regulating chondrocyte hypertrophy and chondrocyte maturation in the growth plate. Two decades of research support the concept of SHOX as a transcription factor that integrates diverse aspects of bone development, growth plate biology, and apoptosis.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology