Short stature affects approximately 2-3 % of children. It represents one of the more common conditions for which clinical attention is sought during childhood. A relatively frequent cause of genetically determined short stature is the deficiency of the SHOX protein. SHOX is required for normal growth via regulation of skeletal development. It is estimated that mutations affecting the SHOX-gene are the underlying cause for short stature in 5% of the cases. The mutations result in a wide spectrum of short stature phenotypes, including symptoms of Turner syndrome (TS), Leri-Weill syndrome (LWS), short stature without any specific features (idiopathic short stature, ISS) and Langer mesomelic dysplasia (LMS).

SHOX is located in the pseudoautosomal region (PAR1) of the X and Y chromosomes. About 77% of the mutations are deletions in the SHOX critical region. Point mutations can also occur as a molecular cause of short stature, thus for cases with excluded deletion a sequence analysis has to be performed.

A world-wide clinical study has shown a beneficial effect on growth of children affected with SHOX-deficiency by administration of human growth hormone (GH). Based on this study, GH substitution has been FDA approved for these patients. A prerequisite for the treatment with GH is the molecular analysis of SHOX and detection of an alteration affecting this gene. Thus, the genetic testing of SHOX for patients with short stature can be considered as a typical example for personalized medicine.

The detection rate of deletions is varying between the different laboratories offering the diagnostics because of the various techniques that are applied. EMQN is offering a pilot scheme for SHOX testing in 2011 - there is no fee for participation if you register in fee period 1.