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 22.1 (23.7 to 20.4), 22.7 (25.0 to 21.0), and 21.6 (23.0 to 0.0), respectively. At presentation, height, HC, and serum IGF-1 SDSs were 23.0 (25.5 to 21.7), 22.5 (24.2 to 20.5), and 11.2 (21.3 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 5 12) and 2 (n 5 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.,
Journal of Clinical Endocrinology and Metabolism
Department of Pediatrics

Walenkamp, M., Robers, J.M.L., Wit, J., Zandwijken, G., van Duyvenvoorde, H., Oostdijk, W, … Losekoot, M. (2019). Phenotypic Features and Response to GH Treatment of Patients With a Molecular Defect of the IGF-1 Receptor. Journal of Clinical Endocrinology and Metabolism, 104(8), 3157–3171. doi:10.1210/jc.2018-02065