ESPE Abstracts

Background: In patients with SHOX deficiency, radiographic abnormalities can vary, with some cases showing no deformities or only mild deformities, particularly in young children, while Madelung deformity is the most commonly observed radiographic feature. Growth hormone (GH) therapy for individuals with SHOX deficiency has been available in Japan since June 2023. This report summarizes a case series of SHOX deficiency diagnosed at a single institution, with a focus on radiographic changes from childhood to adolescence and the response to GH therapy.

Cases: We reviewed seven cases of SHOX deficiency in patients aged three to sixteen years who were referred to our institute for evaluation of short stature between 2007 and 2021. Diagnosis of SHOX deficiency was confirmed by genetic analysis, revealing three cases of gene deletions, one case of gene duplication, one case of a heterozygous missense variant, one case of a homozygous variant, and one case of mosaicism. Radiographs at diagnosis showed abnormalities in four patients, two of whom had both bowing of radius, and triangularization of the distal radial epiphysis, and two of whom had only bowing of radius. Three patients had no radiographic abnormalities. 5 patients were treated with GH, 3 of them in the study. All patients were treated with GH at a dose of 0.35 mg/kg/week. The height SDS before the start of GH treatment was -2.5--2.0 SD. After 24 months from the start of GH treatment, the height SDS of 4 patients increased by 0.8-1.8. One case could not be evaluated due to the short observation period after GH treatment.

Discussion: Among these cases diagnosed with SHOX deficiency by molecular analysis, about half of them had no abnormal radiographs at the time of diagnosis. As previously reported, only one case was diagnosed before school age. In this case, triangulation, which is considered to be relatively common even in young children, was observed, leading to the diagnosis. SHOX deficiency was reported to be present in 1-17% of cases diagnosed as idiopathic short stature, and it should be noted that some cases do not present with radiographic abnormalities at the time of diagnosis. In our cases, the response to GH treatment was good. It becomes essential to reach an early definitive diagnosis to begin an early GH treatment, and molecular analysis might be considered in cases with suspected of SHOX deficiency earlier, even if there are no radiographic features.