Importantly, both RA4 and Pen display a fore- and hindlimb activity when assayed in transgenic reporter approaches, and indeed, in the Liebenberg syndrome, the Pitx1 gene gets endo-activated, i.e. ectopically activated by one of these two enhancers, Pen, in developing forelimbs4. This evidence concerns the gene PITX1 and Brachydactyly - elbow wrist dysplasia.