Endocrine Abstracts

Background: Insulin-like growth factor-1 (IGF-1) acts via the type 1 IGF receptor (IGF1R), located on chromosome 15q26.3, and plays a crucial role in normal intrauterine and postnatal growth. Heterozygous 15q26.3 deletions can cause intrauterine and postnatal growth retardation, microcephaly, and developmental delay. Very few cases have been reported in the literature with a variable response to recombinant human growth hormone (rhGH) treatment. We report the effect of rhGH treatment in a child with 15q26.3 deletion encompassing the IGF1R.

Case: The patient was delivered at 36 weeks of gestation and was small for gestational age with a birth weight of 1.95 kg (<3rd percentile). Postnatally, the patient exhibited mild hypotonia and required feeding support. He also has microcephaly, dysmorphic features, and motor developmental delay. Chromosomal microarray analysis revealed a 1.89 Mb interstitial deletion of the long arm of chromosome 15 at band 15q26.3, encompassing the IGF1R gene. At 30 months, the patient’s length was at the 0.4th percentile, while the mid-parental height was at the 9th percentile. Mother was also on the shorter side and subsequent genetic analysis indicated the deletion was maternally inherited. The patient’s IGF1 level was 6 nmol/l, with IGF-BP3 at 2.7 mg/dL. Initially, rhGH was initiated at 1 mg/m²/day. However, the height velocity in the first year was 3.1 cm/year despite good compliance and an IGF1 level of 31.6 nmol/l. Subsequently, the dose was increased to 1.2 mg/m²/day, resulting in satisfactory growth. At four years of age, the patient’s growth velocity increased to 10 cm/year, placing his height at the 9th percentile. Following commencement of rhGH, a mean height of 0.57 SDS improved over 15 months of time.

Conclusion: This case demonstrates a good response to rhGH therapy, suggesting that GH resistance caused by heterozygous IGFIR deletions can be potentially overcome by GH therapy at higher dose. The long-term treatment improved height SDS, the final adult height will need to be monitored. An individual trial of GH therapy may be appropriate in these patients.