ESPE Abstracts

Background: IGF1 is essential for pre and postnatal growth. Mutations in IGF1 receptor (IGF1R) gene have been described in patients with intrauterine growth retardation and other anomalies.

Objective and hypotheses: To study IGF1R gene in small for gestational age (SGA) patients with short stature and correlate the results with clinical presentation and response to rhGH treatment.

Method: Longitudinal retrospective study of 69 SGA patients with short stature registering weight, height, IGF1 levels, adult height, target height, height at start of rhGH and height gain after treatment. Genetic analysis consisted in DNA amplification, sequencing and electrophoresis. Statistics SPSS V20.0 (P<0.05).

Results: From the total cohort (79.7% female) 10.1% showed mutation in IGF1R (Y487F,pL81Fexon2C>T and (IVS (+30) delGT), 81.4% polymorphisms(E1013E, IVS (+72) A/G, V532V and N608N) and 13% were normal. Patients with mutations were significantly smaller at birth (length: −3.96 SDS, Weight: −2.48 SDS, Cephalic circumference: −2.8 SDS) and presented with familiar short stature. Patients with polymorphisms showed lower length and weight at birth, target height and adult height compared with those with normal IGF1R analysis (NS). Within patients with polymorphisms, those with IVS (+72) A/G initiated before rhGH (6.4±2.6 vs 8.9±2.9 years; P=0.03), with more affected height (−3.32±0.6 vs −2.54±0.6 SDS; P=0.04), lower levels of IGF1 (117±71 vs 264±130 mg/d; P=0.03) l and showed a better response in the first year of treatment (Δ0.94±0.8 vs Δ0.38±0.3 SDS; P=0.01).

Conclusion: IGF1R gene mutations cause severe prenatal growth failure and are usually associated with familiar short stature. Polymorphisms in this gene (E1013E and IVS (+72) A/G) have been found in SGA patients with short stature. The presence of different polymorphisms can influence the response to rhGH treatment in these patients.