Context: Evidence for growth hormone therapy in Indian hedgehog (IHH)-related short stature is limited. Objective: To assess growth outcomes in children with heterozygous pathogenic IHH variants treated with recombinant human growth hormone (rhGH). Methods: Retrospective cohort of 19 children with short stature carrying heterozygous deleterious IHH variants treated with daily rhGH (33–50 µg/kg/day); 10 attained adult height. Outcomes were height SD score (SDS), height velocity, and adult height SDS. Results: At treatment start, median height SDS was −2.6 (IQR: −3.0; −2.2) and height velocity 5.1 cm/year (IQR: 4.3; 6.2). After 1 year, height velocity increased to 9.2 cm/year (IQR: 7.9; 10.3) and height SDS to −1.9 (IQR: −2.3; −1.6), with Δheight SDS 0.7 (IQR: 0.5; 1.0). Over a median of 4.0 years of therapy (IQR: 3.4; 5.7), total Δheight SDS was 1.2 (IQR: 0.8; 1.5), and 16/19 (84%) had height SDS ≥ −2.0 at last follow-up. At last follow-up, patients with predicted loss-of-function variants (n=6) showed higher height SDS than those with missense variants (n=13) −0.8 (IQR: −0.9; −0.7) vs −1.7 (IQR: −1.9; −1.6) and greater Δheight SDS 1.4 (IQR: 1.2; 1.9) vs 0.8 (IQR: 0.7; 1.3). Among those reaching adult height, adult height SDS was −1.7 (IQR: −1.9; −1.6) after a median of 5.8 years of therapy (IQR: 4.0; 7.3), with Δheight SDS 0.8 (IQR: 0.7; 1.4). Conclusions: rhGH therapy was associated with clinically meaningful height gains, including adult height improvement, in children with IHH-related short stature; variant class may modify response.
Cavalcante et al. (2026) studied this question.