The identification of the SHOX (short stature homeobox) gene in the pseudoautosomal region (PAR) of the X and Y chromosomes was a significant advance in linking dosage effects with specific genetic factors [Clement-Jones et al., 2000]. The SHOX gene is a transcription factor whose decreased expression in 46,XO was demonstrated through deletion studies as being at least partially responsible for the characteristic short stature and skeletal abnormalities. It is thought that excessive copies of the SHOX gene may be responsible for the increased height characteristic of SCAs with additional chromosomes [Kanaka-Gantenbein et al., 2004; Aksglaede et al., 2007b]. Although some of the increased height in 47,XXY may be related to hypogonadism delaying the closure of the epiphyseal growth plates, the observations that taller stature is present well before puberty and is also present in SCAs not associated with hypogonadism such as 47,XXX and 47,XYY suggests genetic dosage effects likely also contribute.
