Endocrine Abstracts

JOINT3865

Introduction: C-Type Natriuretic Peptide (CNP) and its receptor (NPR-B) are important paracrine factors regulating longitudinal bone growth. Homozygous or compound heterozygous loss-of-function mutations in the NPR2 gene lead to "Maroteaux Type Acromesomelic Dysplasia, " while heterozygous loss-of-function variants cause "Miura Type Epiphyseal Chondrodysplasia" and "Short Stature Without Specific Skeletal Anomalies. "

Methods: Patients diagnosed with idiopathic short stature and carrying a heterozygous NPR2 gene variant who received growth hormone (GH) therapy at the Pediatric Endocrinology Clinic of Gazi University were included. Patients with chronic diseases, medication use affecting growth, or irregular follow-ups were excluded. Data were obtained from clinic records.

Results: Among 19 patients with NPR2 heterozygous variants, 9(47. 3%) received GH therapy; 44% (n = 4) were female. The mean birth weight was 2750±892g, with a mean birth weight SDS of -0. 51±1. 52. The mean age at presentation was 9. 1±3. 7years, with a height of 117. 5±21. 8cm and height SDS of -2. 5±0. 54. Parental height SDS values were -1. 89±0. 83 for mothers and -2. 6±1. 2 for fathers. The mean annual growth velocity was 4. 3±0. 78cm. GH stimulation test results were insufficient in 5 patients (55. 6%). The mean GH initiation age was 9. 9±1. 7years, with an initial height of 122. 3±11. 5cm and height SDS of -2. 5±0. 48. Initial and maximum GH doses were 0. 033±0. 004mg/kg/day and 0. 040±0. 006mg/kg/day, respectively. The mean annual growth velocity during GH therapy was 7. 6±1cm/year, showing a significant difference from pre-treatment values (P = 0. 01). The mean GH therapy duration was 2±1. 6years. At the last follow-up, the mean age was 12. 2±2. 3 years, height was 141. 2±14. 2cm, and height SDS was -2±0. 4. Predicted height before GH therapy was 154. 6±6. 7cm (149. 6±8. 4cm for females, 157. 7±3. 5cm for males), while post-treatment predicted height was 157. 1±7. 4cm (150. 1±5cm for females, 161. 2±35. 1cm for males). Although the difference was not statistically significant, an increase in predicted height was observed.

Discussion/Conclusion: Heterozygous NPR2 variants are associated with short stature and non-specific clinical findings. This study represents the largest cohort of NPR2 heterozygous patients receiving GH therapy. In this study, GH therapy significantly improved growth velocity in proportionate short stature patients with NPR2 variants. One patient exhibited low growth velocity, which may be attributed to delayed treatment initiation, pubertal status, and advanced bone age. Although final height has not been reached, increased growth velocity and predicted height were observed. GH therapy should be considered for children with heterozygous NPR2 variants and short stature. However, long-term and larger studies are required to assess treatment efficacy.