The downregulation of Runx2 expressing FLNBT1616A in our research demonstrated that c.4846A>G (p.T1616A) variant could aggravate skeletal manifestations of our VDDR proband by impairing osteogenesis, while the upregulation of Runx2 in cells expressing FLNBI2341R observed could explain the early closure of epiphyses in our LRS proband. This evidence concerns the gene RUNX2 and Larsen syndrome.