ESPE Abstracts

Shox gene deficiency which causes short stature is a known indication for treatment with growth hormone. The prevalence of shox deficiency among children with idiopathic short stature has a high variability in different studies and ranges between 1.5-17%. We aimed to determine the incidence of SHOX haploinsufficiency in our region and to assess the genotype-phenotype relation which may help with setting criteria in the decision to which patients should we offer this genetic testing.

Methods: This was a prospective study of patients with idiopathic short stature who had disproportionate stature. In order to find changes in the Shox gene, every blood sample was tested by two methods: First, gene sequencing in order to identify point mutations, and thereafter MLPA testing was carried out to diagnose copy number variations. The second stage of the research examined the clinical characteristics of the patients for the purpose of checking genotype-phenotype correlation.

Results: Shox haploinsufficiency was found in two out of the 24 patients (8 adults, 16 children) after testing by the MLPA method. Gene sequencing was found intact among all those tested. The prevalence of Shox gene haploinsufficiency was 8.3%. In comparing the phenotypical characteristics between the patients with Shox haploinsufficiency as opposed to patients who were not found to have this gene deficiency the average height SDS is -2.6 according to age and sex in both groups (P=0.939). Shox patients were found to have a statistically significant higher sitting height to standing height ratio (P=0.017). Likewise, upper to lower segment ratio was significantly higher among Shox patients (P=0.017). These parameters express the unique characteristics of Shox haploinsufficiency short stature which presents with mesomelic short stature. Nevertheless, we did not find a significant difference in the arm span to height ratio between the two groups. (P=0.19)

Conclusions: There is great importance in diagnosing shox gene deficiency as a cause for short stature. As was demonstrated in this study the prevalence of shox haploinsufficiency is not insignicant and further research, with wider scope is needed. Using special criteria based on the mesomelic short stature characteristics can pinpoint the suspected patients who need genetic evaluation for shox deficiency and further genetic counselling. Examining family history where only some members suffer from short stature can strongly suggest the presence of monogenic hereditary disorder. The research emphasizes the importance of using the MLPA method in order to assess the presence of shox gene deficiency.