Background: Mutations of the Short Stature Homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes(Xp22 and Yp11.3) are correlated with short stature. Patients with SHOX-Deficiency (SHOX-D) have different degrees of growthimpairment and generally remain short in adulthood. Turner Syndrome (TS) subjects present a SHOX haploinsufficiency that appears to be substantially responsible for their short stature. Considering the positive effects obtained with GH therapy in patients with TS, this treatment was also proposed in short stature due to isolated SHOX-D.Objective: The aim of our retrospective study was to analyze height gain and safety of rhGH therapy in patients with SHOX-D.Methods:We studied twelve patients (7 females, 5 males; age 8.7 ± 2.9 years; range 4.9-13.16 years)) with isolated SHOX-D geneticallyconfirmed, all with height SDS < 1.5, target height SDS -1.29 ± 0.65, and in 1 patient with SHOX-D combined with trichorhinophalangealsyndrome. All patients were treated for at least 1 year (2.49 ± 1.45; range 1-6.43) with rhGH (mean dosage of 0.026 ± 0.003mg/kg/day). Results:: GH treatment significantly improved Growth Velocity SDS (2.11 ± 1.42) and height SDS (from -2.03 ± 0.22 to -1.62 ± 0.45, p<0.03), without affecting BMI SDS (from 0.18 ± 1.06 to 0.45 ± 1.74). In the patient with SHOX-D and trichorhinophalangeal syndrome GH failed to improve height SDS. Madelung deformity, if present at the start of therapy, did not deteriorate during follow-up. The better catch-up growth was obtained in the 3 younger patients. There were no discontinuation due to adverse events and no serious adverse events were reported for subjects with SHOX-D.Conclusions: The growth velocity in subjects with SHOX-D was significantly accelerated during rhGH therapy and resulted in a significant gain of height. Our data confirm the few reported evidences showing that GH therapy has a positive statural effect in SHOX haploinsufficiency without cause serious adverse events. Further longitudinal studies are needed to confirm these preliminary results
