ESPE Abstracts

Background:Short stature may be due to various pathological conditions or may be idiopathic. SHOX (Short Stature Homeobox on X chromosome) gene is involved in the regulation of skeletal growth and is a main cause of short stature on monogenic basis. The frequency of this condition in children with idiopathic short stature (ISS) was reported to range from 2 to 17%. The phenotypic spectrum is heterogeneous, varying from Léri-Weill dyschondrosteosis (LWD) to Langer's mesomelic dysplasia (LD) and ISS. The main characteristics associated with this condition, such as mesomelia of the limbs and Madelung's deformity, develop over time and usually appear during the second decade of life, especially in women. The use of recombinant growth hormone (rGH) for SHOX deficiency was approved from 2006 in USA and from 2014 in Europe. The aims of this study were to analyze the frequency and type of alterations of the SHOX gene in a population of children with short stature, and the response to rGH therapy

Patients and methods: All patients with molecular diagnosis of SHOX deficiency were retrospectively selected from a total group of 747 children with ISS. Auxological parameters at birth and at the time of diagnosis were analyzed, In addition, response to rGH treatment was assessed in a subgroup of patients reaching 36 months of follow-up. Gentic diagnosis was made by sequencing and MLPA analysis of SHOX gene and its regulatory sequences.

Results: Pathogenetic variants in the SHOX gene were found in 82/747 children (11%). Unlike other series, the most frequent mutations were exonic variants. Therapy with rGH determined a significant increase in both growth velocity and height after 36 months (average increase of +3.60 SDS and +0.85 SDS, respectively).

Conclusions: Present data confirm that SHOX deficiency is a relevant cause of ISS. The different frequency of mutations in this series compared to other populations may be related to a different genetic background. Treatment with rGH is able to improve growth pattern in these children. Early diagnosis permits better catch-up growth. The type of genetic alteration does not influence the response to therapy, even if further studies with a larger sample size are needed.