ESPE Abstracts

Background: The IGF1 receptor (IGF1R) gene is located on the distal long arm of chromosome 15 (15q26.3). Heterozygous inactivating mutations of the IGF1R gene cause intrauterine and postnatal growth failure and mental retardation.

Objective: The purpose of this research is to determine the most effective GH treatment for patients with IGF1R haploinsufficiency due to heterozygous deletion.

Method: We investigated the clinical course of four patients with IGF1R haploinsufficiency due to heterozygous deletion diagnosed by array CGH analysis.

Results: All four patients were born with severe intrauterine growth failure. One female patient at 7 years of age, with height 101.3 cm (−4.2 SD), was administered 0.18 mg/kg per week of GH and increased to 0.20 mg/kg per week. Her serum IGF1 was 375 ng/ml before GH treatment. Her adult height was 141.1 cm (−3.2 SD). During GH treatment, high levels of IGF1 persisted (380–730 ng/ml before the development of secondary sexual characteristics and 648–1030 ng/ml since then. The other three patients (two female and one male) at 3 years of age, with height SDS ranging from −4.7 SD to −6.4 SD, were administered 0.25 mg/kg per week of GH and increased to 0.35–0.47 mg/kg per week. The serum IGF-1 was 128–260 ng/ml before GH treatment. One female patient improved from −6.4 SD to −3.5 SD after 5 years of GH treatment. Her maximum IGF1 was 877 ng/ml during GH treatment. The male patient improved from −5.1 SD to −4.1 SD after 1 year of GH treatment. His maximum IGF1 was 513 ng/ml during GH treatment. The other female patient improved from −4.7 SD to −1.9 SD after 4 years of GH treatment. Her maximum IGF1 was 701 ng/ml during GH treatment. However, there was no obvious improvement of mental retardation in the four patients.

Conclusion: Long-term GH therapy causes growth acceleration during childhood in a dose-dependent manner. Earlier onset of therapy may provide better results.