Detection of SHOX Gene Variations in Patients Who Had Skeletal Abnormalities With/Without Short Stature.

Objective: SHOX gene is one of the genetic causes of short stature and the clinical phenotype includes variable degrees of growth impairment such as Langer mesomelic dysplasia, Leri-Weill dyschondrosteosis or idiopathic short stature. In this study, we aimed to describe the clinical features and molecular results of SHOX deficiency in a group of Turkish patients who had skeletal findings with/without short stature. Methods: Fourty-six patients with idiopathic short stature, disproportionate short stature or skeletal findings without short stature from 35 different families were included in the study. SHOX gene analysis was performed using Sanger sequencing and MLPA analysis. Results: We detected three different point mutations (two nonsense, one frameshift) and one whole SHOX gene deletion in 15 patients from 4 different families. While 4 of 15 patients had Langer mesomelic dysplasia, the remaining patients had clinical features compatible with Leri-Weill dyschondrosteosis. Madelung's deformity, cubitus valgus, muscular hypertrophy and short forearm were the most common phenotypic features as well as short stature. Additionally, hearing loss was also detected in 2 patients with Langer mesomelic dysplasia. Conclusion: In this study, we presented the clinical spectrum and molecular findings of 15 patients with SHOX gene mutations or deletions. SHOX deficiency should be especially considered in patients who have disproportionate short stature or forearm anomalies with/without short stature. Although most of the patients had a partial or whole gene deletions, SHOX gene sequencing should be performed in suspected cases. Furthermore, conductive hearing loss may rarely accompany these clinical manifestations.