Endocrine Abstracts

JOINT2429

Introduction: The IGF1 and IGF1R genes regulate prenatal and postnatal growth processes. Mutations in the IGF1R gene can cause intrauterine growth restriction (IUGR), postnatal growth retardation, microcephaly, intellectual disability, neurodevelopmental issues, and brain and cardiac anomalies. Biallelic mutations generally result in more severe phenotypes than heterozygous mutations. IGF1R mutations are a significant etiological factor in patients with small gestational age (SGA) and growth retardation. Genetic analysis of these mutations is critical for early diagnosis and treatment strategies.CaseReportThis report describes a 1-year-4-month-old male patient born SGA (38th week, 1975 g, −3.76 SD) with ongoing growth retardation. The birth length was 45 cm (−2.19 SD), and the calculated mid-parental height was 171.2 cm (−0.81 SD). No consanguinity was identified. Physical examination revealed a height of 72.5 cm (−2.7 SD), body weight of 6.8 kg (−4.09 SD), and head circumference of 43.5 cm (−3.12 SD). Testicular volume was 2/2 ml and penile length were normal for his age. Liver, kidney, and thyroid function tests were normal, and celiac autoantibodies were negative. At the time of the patient’s admission, IGF1 levels were measured at 46.1 ng/ml (−1 SD), and IGFBP3 levels at 3008 ng/ml (+1 SD). No abnormalities were observed during blood glucose monitoring. Nutritional support was initiated due to malnutrition, but growth velocity remained insufficient. Genetic analysis identified a heterozygous c.3595G>A p.(Gly1199Arg) variant in the IGF1R gene, also detected in the mother. Although growth hormone therapy was recommended, the family declined treatment.

Discussion: Mutations in IGF1R lead to phenotypes resembling IGF1 deficiency but require different therapeutic approaches. The IGF1 receptor regulates growth, metabolism, and cell survival via the MAPK/ERK and PI3K → AKT pathways. IGF1R defects may mimic Silver-Russell or SHORT syndrome phenotypes, with microcephaly as a distinguishing feature. Walenkamp et al. proposed a clinical scoring system for IGF1R mutations based on low birth weight, small head circumference, short stature, and elevated IGF1 levels. Recombinant growth hormone (rGH) therapy’s efficacy in IGF1R mutations remains unclear. Studies report modest height gains (average 1.0 SDS) with rGH but caution against dose escalation due to high IGF1 levels. The genotype-phenotype correlation for IGF1R mutations remains unresolved. Heterozygous carriers typically exhibit milder phenotypes than homozygous individuals. This case represents the first Turkish pediatric patient with the IGF1R Gly1199Arg variant.

Keywords: IGF1R mutation, SGA, Microcephaly, Recombinant growth hormone