Background: Short stature caused by point mutations or deletions of the short stature homeobox (SHOX) gene (SHOX haploinsufficiency, SHI) is a registered indication for growth hormone (GH) treatment. Patients with a SHOX enhancer deletion (SED) have a similar phenotype, but their response to GH is unknown. It is uncertain if duplications of SHOX or its enhancer (SDUP) can cause short stature.
Objective and hypotheses: To describe the clinical characteristics and growth response to GH treatment in patients with aberrations of SHOX and its enhancers.
Method: In this retrospective observational multi-center study (2002March 2014) clinical information was available from 130 patients (72 SHI, 44 SED, 14 SDUP) and from 52 patients treated with GH. Height, sitting height, arm span, dysmorphic features and indicators of the growth response to GH (delta height SDS, height velocity and index of responsiveness) were collected.
Results: Patients with SEDs showed similar height SDS to patients with SHI (−2.3 and −2.6 respectively, P=0.2) and have a similar frequency of Madelung deformity, but they were less disproportionate (sitting height/height ratio SDS 2.0 vs 3.1 (P<0.01), and extremities-trunk ratio 2.57 vs 2.43 (P=0.03)). Parents carrying SEDs are less short and disproportionate than parents with SHI. Height SDS and body proportions varied widely in both groups. The first year growth response to GH treatment was significantly greater in prepubertal patients with SEDs than SHI. None of the patients with a SDUP was disproportionate and SDUP cosegregated poorly with short stature; their growth response to GH treatment (n=3) was similar to the other groups.
Conclusion: This is the first study to assess the effect of GH in patients with SEDs. Patients with SEDs are equally short, but less disproportionate than patients with SHI, and show a greater response to GH treatment.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology