ESPE Abstracts

Introduction: Hypochondroplasia (HCH) is a form of mild dwarfism caused by heterozygous gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3). FGFR3 is a negative regulator of endochondral bone growth, and individuals with HCH typically exhibit characteristics such as disproportionate short stature with shortening limb length, lumbar lordosis, and macrocephaly. Regarding recombinant human growth hormone (rhGH) therapy in children with HCH, data are scarce and often limited to short treatment periods, with little information available about the impact on adult height.

Objective: This study aimed to assess the response to rhGH treatment in children with Hypochondroplasia.

Methods: Ten patients (6 males; 4 females) clinically and genetically diagnosed with HCH and rhGH therapy for short stature for at least one year were selected for this study. The outcomes were changes in growth velocity (GV) and height SDS for the reference population.

Results: At the start of the treatment, the mean calendar and bone age were 8.6±2.7 and 7.9±3.4 years, respectively. Two patients were pubertal. The mean height-SDS was -3.1±1.0 for the reference population. All patients received daily rhGH at a mean dose of 40±8.6 µg/kg/d. The GV SDS increased from baseline values of -2.2 ±2.2 to 0.7±1.9 in the 1st year of therapy, an increment of 2.2±1.9 cm (P = 0.014). Height SDS after the 1^st year was -2.9±0.9, with no significant improvement (P = 0.607). Two more patients became pubertal. After a mean duration of therapy of 2.9±1.7 years, six patients discontinued the treatment with rhGH. No increment in height SDS was observed at the end of treatment compared to the start of therapy (from -3.5±1.0 to -3.3±1.0; P = 0,731) even with a higher dose of rhGH (mean dose of 46.7±6.7 µg/kg/d). Five patients achieved adult height without an improvement after a mean duration of 3.3 years of rhGH treatment (height-SDS changed from -3.5±1.1 to -4.0±1.1; P = 0.442). The predicted adult height SDS was -3.8±1.6 at the beginning of therapy.

Conclusion: Limited data exist on the use of rhGH therapy in Hypochondroplasia. In the present study, we did not observe an increment in height SDS either during the first year of treatment or during the follow-up. We conclude that rhGH therapy was not efficient in improving adult height of patients with HCH. Alternative therapies should be considered for the treatment of short stature in children with HCH.