Endocrine Abstracts

JOINT690

Background: Insulin-like growth factor 1 receptor (IGF1R) mutations are rare genetic variants associated with growth failure due to impaired IGF1 signaling. We report a family with a novel likely pathogenic IGF1R mutation presenting with short stature, elevated IGF1 levels, and suboptimal growth response to growth hormone (GH) therapy.

Case Presentation: A 4-year-old boy born at 37+1 weeks by cesarean section with a birth weight of 2210 g (SGA) presented with short stature below the 3rd percentile. GH stimulation testing revealed a peak GH level of 13.7 ng/ml, indicating normal GH secretion. Initial IGF1 levels were significantly elevated at 202 ng/ml (reference range: 26.8–134 ng/ml for 4-year-old boys). Genetic analysis using a short stature NGS panel identified a heterozygous likely pathogenic IGF1R mutation (c.16G>A, p.Glu56Lys). Despite starting GH therapy (0.23 mg/kg/week), the patient showed a poor growth velocity, and his height percentile remained below the 10th percentile. The proband’s 8-year-old sister, who had been treated for idiopathic short stature (ISS) with GH therapy since the age of 5, exhibited persistently elevated IGF1 levels (576 ng/ml) without achieving height above the 10th percentile. Genetic testing confirmed the same IGF1R mutation. Their mother, with a height of 148 cm, was also found to carry the heterozygous mutation.

Conclusion: This family highlights the clinical characteristics of a novel IGF1R mutation, including short stature, elevated IGF1 levels, and suboptimal response to GH therapy. These findings underscore the importance of genetic evaluation in patients with short stature and poor response to GH treatment. Further functional studies of the c.16G>A, p.Glu56Lys variant are needed to understand its impact on IGF1 signaling and growth