By measuring copy number variants in 816 clubfoot probands, we identified duplications of chromosome Xp22.33 involving the SHOX gene and surrounding regions in 1.1% of cases compared to 0.07% of controls. These duplications are likely causative in some cases, as four out of six SHOX duplications were not present in the unaffected parents but were confirmed in the proband, resulting in a de novo rate of 66% (4/6) for chromosome Xp22.33 duplications. This will have immediate and direct impact on patient care because these genetic abnormalities can easily be detected with clinically available chromosomal microarray studies. (https://jmg.bmj.com/content/early/2020/06/09/jmedgenet-2020-106842 )