Novel IGF1R Variants in Short Stature: Lessons from Two Patients and Outcome of Growth Hormone Therapy

• DOI: 10.4274/jcrpe.galenos.2025.2024-12-7
• Publication Date: 2025-04-24T07:00:36Z
• Authors: Mehmet Eltan; Hilal Sekizkardes; Sezin Canbek; Murat Hakki Yarar; Saygin Abali; Zehra Yavas Abali
• Keywords: Idiopathic short stature

The growth hormone (GH) - insulin-like factor 1 (IGF1) axis is essential for the regulation of growth. IGF1 exerts its effects through receptor (IGF1R) that plays a pivotal role in fetal and postnatal Pathogenic monoallelic IGF1R variants are known to cause pre- restriction, often accompanied by normal or elevated serum levels. Herein, clinical genetic characteristics two cases with novel variants, emphasizing their patterns, endocrinological findings, response recombinant human (rhGH) therapy. first case, 6.3-year-old boy, had birth weight 2,500 g (-2.5 SDS) current height 101.5 cm (-3.2 SDS). Laboratory investigations revealed IGFBP3 levels 117.8 ng/ml (0.9 4.55 µg/ml (1.3 SDS), respectively. Clinical exome sequencing (CES) identified heterozygous c.3722+1G>A/p.(?) variant (NM_000875.5) inherited from mother. At 6.9 years age, rhGH treatment was initiated at dose 0.035 mg/kg/day. patient has been receiving years, achieving gain +0.3 SDS per year, an uneventful follow-up. second case features 3-year-old male short stature history being born small gestational age (SGA) (-2.6 His were 70.0 (-2.1 8.8 kg (-1.1 He frequent respiratory infections. Pituitary normal, he no evidence GH deficiency. CES c.2275_2278 dup/p.(Ala760Glyfs*21) IGF1R. Uncovering causes idiopathic SGA crucial, as it facilitates more precise diagnoses, reduces unnecessary testing, potentially enables targeted therapies. Our experience therapy one suggests modest response, consistent previous studies. However, during highlight importance balancing therapeutic doses optimize gains without causing side effects.