ESPE Abstracts

Introduction: The SHOX (short stature homeobox) gene, located in the pseudoautosomal region of the X and Y chromosomes, implicated in Leri-Weill dyschondrosteosis, Langer mesomelic dysplasia, idiopathic short stature. Growth hormone (GH) therapy has proven effective in promoting height gain in patients with SHOX deficiency. We will present a case who was treated for borderline precocious puberty and diagnosed with Leri-Weill dyschondrosteosis upon admission to our clinic in the following years, started on GH treatment.

Case Presentation: A 12.5-year-old female presented with progressive deformities in both wrists. She was born at term, weighing 3960 grams, measuring 52 cm in length. At age 8, she was diagnosed with precocious puberty, treated with GnRHa, which ceased at age 10.5. There was no consanguinity between her parents. On physical examination, her height was 149.6cm (-0.65SDS), weight was 53.1 kg (0.85SDS), and BMI was 23.73 kg/m² (1.38SDS). Her mother’s height was 165 cm (0.32 SDS), her father’s height was 170cm (-1.01SDS), and her target height was 161cm (-0.36SDS). She was at Tanner stage 4 of puberty. The patient has mesomelia and trunk/extremity ratio of 1.28(>+2SDS). She had noticeable Madelung deformity in both wrists. Bone age was at 13 years, with a predicted adult height of 151cm (-2.06SDS). Laboratory tests including hemogram, liver and kidney function, thyroid function, gonadotropin levels were normal, IGF-1 was 482ng/mL (+1/+2SDS). Genetic analysis revealed a 46 XX karyotype, a deletion in the SHOX gene detected by FISH analysis. Segregation analysis found a deletion in the SHOX gene region Yp11.32 in her father. With approval for off-label use, GH therapy was initiated at a dose of 0.35 mg/kg/week. After three months of treatment, her height increased by 4.1 cm to 153.7 cm (-0.32 SDS). As IGF-1 increased to 842 ng/mL (>2 SDS), the GH dose was reduced to 0.25 mg/kg/week. Despite this adjustment, IGF-1 levels remained above 2 SDS, necessitating a temporary cessation of therapy. Once IGF-1 levels fell to +1/+2 SDS, therapy resumed at 0.2 mg/kg/week. In the 6th month of follow-up, the treatment of the patient, who had no height increase and a bone age of 14, ceased.

Conclusion: GH therapy has a positive effect on height in patients with SHOX deficiency. Madelung deformity, as observed on wrist radiographs, can initially present with subtle signs and may be overlooked. Regular monitoring of IGF-1 levels is crucial during GH therapy to ensure safety and efficacy.