Phenotypic Features and Response to GH Treatment of Patients With a Molecular Defect of the IGF-1 Receptor

Abstract Context The phenotype and response to GH treatment of children with an IGF1R defect is insufficiently known. Objective To develop a clinical score for selecting children with short stature for genetic testing and evaluate the efficacy of treatment. Design and Setting Case series with an IGF1R defect identified in a university genetic laboratory. Patients and Interventions Of all patients with sufficient clinical data, 18 had (likely) pathogenic mutations (group 1) and 7 had 15q deletions including IGF1R (group 2); 19 patients were treated with GH. Main Outcome Measures Phenotype and response to GH treatment. Results In groups 1 and 2, mean (range) birth weight, length, and head circumference (HC) SD scores (SDSs) were −2.1 (−3.7 to −0.4), −2.7 (−5.0 to −1.0), and −1.6 (−3.0 to 0.0), respectively. At presentation, height, HC, and serum IGF-1 SDSs were −3.0 (−5.5 to −1.7), −2.5 (−4.2 to −0.5), and +1.2 (−1.3 to 3.2), respectively. Feeding problems were reported in 15 of 19 patients. A clinical score with 76% sensitivity is proposed. After 3 years of GH treatment [1.1 (0.2) mg/m2/d] height gain in groups 1 (n = 12) and 2 (n = 7) was 0.9 SDS and 1.3 SDS (at a mean IGF-1 of 3.5 SDS), less than reported for small for gestational age (1.8 SDS). Conclusion A clinical score encompassing birth weight and/or length, short stature, microcephaly, and IGF-1 is useful for selecting patients for IGF1R analysis. Feeding problems are common and the growth response to GH treatment is moderate. A clinical score (based on birth size, height, head circumference, and IGF-1) can select patients for IGF1R analysis. The response to GH therapy is moderate in carriers of heterozygous IGF1R defects.