Endocrine Abstracts

JOINT2922

Introduction: NPR2 and ACAN gene variants are well recognised causes of idiopathic short stature (ISS). Both genes play a crucial role in growth plate regulation; NPR2 through paracrine function of endochondral ossification, while ACAN is a major structural component of the extracellular matrix in cartilage. The study aimed to evaluate and compare the efficacy of growth hormone (GH) therapy in children with NPR2 and ACAN variants.

Methods: Next-generation sequencing was performed in ISS children to identify causal NPR2 and ACAN variants. Eligible children met national guidelines for treatment with GH. The main outcome measure was change (Δ) in height SD score (HtSDS). Comparison was made between:

• Treated and untreated NPR2/ACAN children

• Prepubertal vs. pubertal children receiving GH

• Overall NPR2 vs. ACAN patient outcomes.

Results: A total of 16 NPR2 (11 males) and 17 ACAN (8 males) children were enrolled. Among them 8/16 NPR2 (6 males, mean age 9. 5± 3. 8 years) and 10/17 ACAN (5 males, mean age 8. 2± 3. 2 years) children received GH (treatment duration: NPR2 3. 2±1. 7 years, ACAN 5. 3± 2. 2 years). In the untreated subgroups, the mean Δ in HtSDS was +0. 07 (NPR2) and -0. 23 (ACAN). Children who started treatment at the prepubertal stage (5/8 NPR2, 6/10 ACAN) had greater height gains (Δ HtSDS; +1. 01 in NPR2 and +1. 35 in ACAN) than those who started in puberty (Δ HtSDS; +0. 37 in NPR2 and + 0. 3 in ACAN).

Overall, mean height gain in treated children was:

• NPR2: + 0. 8±0. 4 (mean Δ HtSDS 0. 3±0. 2 per year)

• ACAN +0. 9±0. 8 (mean Δ HtSDS 0. 2±0. 1 per year)

Conclusion: GH therapy significantly improved linear growth in both NPR2 and ACAN groups compared to the untreated children; with a more pronounced effect in ACAN children. Early initiation of GH was particularly effective in both groups.