Endocrine Abstracts

JOINT122415

Introduction: Insulin-like growth factor 1 (IGF-1) is essential for prenatal and postnatal growth, acting through the IGF1 receptor (IGF1R), a tyrosine kinase encoded by the IGF1R gene, located on the distal arm of chromosome 15 (15q26.3). Deletions of 15q26 are rare chromosomal abnormalities, typically associated with a variable degree of intrauterine growth restriction (IUGR), postnatal growth failure, developmental delay, microcephaly, intellectual disability, among other congenital anomalies.

Case Report: A five-year-old girl was referred to endocrinology clinic for short stature. Family history revealed a short stature mother (147.5 cm, -2.42 SDS) and an otherwise normal-height family, without consanguinity. Pregnancy was uneventful until 34 weeks of gestation, when IUGR and microcephaly were detected. A C-section was performed at 35 weeks and 5 days. Birth somatometry: height 42.7 cm [-1.5 standard deviation score (SDS)], weight 1930 g (−1.40 SDS) and head circumference 29.5 cm (-1.6 SDS). Due to prenatal ultrasound findings, genome-wide array analysis was performed in cord blood. A 214 kb terminal deletion at a single copy of 15q26.3 was reported, resulting in a partial deletion of IGF1R. She was followed-up at general paediatrics, with a height around -2 SDS until 12 months. She was lost to follow-up during COVID-19 pandemic. From three-years-old on, the height has been around -3 SDS. At the first visit: height 96.3 cm (-2.78 SDS), weight 12.4Kg (-2.83 SDS) and BMI 13.4kg/m² (-1.42 SDS). Neither dysmorphic features nor development delay were noted. Growth velocity was 4.3 cm/year. Laboratory investigation showed adequate IGF1 [204.0 ng/ml, reference range (RR): 63.6-250.0] and IGF binding protein 3 (4.14 µg/ml, RR: 2.203-5.202) levels; a female karyotype (46, XX); bone age of 3 years old. The 15q26.3 deletion was also identified in the mother. The patient remains under regular follow-up with the endocrinology team and growth hormone (GH) therapy is being considered.

Discussion: This patient’s findings suggest a partial IGF-1 resistance, resulting in short stature. The deletion at 15q26.3 might explain these findings. Heterozygous mutations typically reduce IGF1R expression or impair signalling, rather than complete receptor loss. The variable phenotype, which is not yet fully understood, presents a management challenge as in our case. The positive effects of GH treatment may result from its direct stimulatory action or elevated IGF-1 levels, which are expected to activate partially insensitive receptors.