Rare and <i>de novo</i> duplications containing <i>SHOX</i> in clubfoot

Abstract

Microduplications of the pseudoautosomal chromosome Xp22.33 region (PAR1) containing <i>SHOX</i> and downstream enhancer elements occur in ~1% of patients with clubfoot. <i>SHOX</i> and regulatory regions have previously been implicated in skeletal dysplasia as well as idiopathic short stature, but have not yet been reported in clubfoot. <i>SHOX</i> duplications likely contribute to clubfoot pathogenesis by altering early limb development.