The IGF1R is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. We detected 21 IGF1R defects in patients with fetal growth restriction, including 8 heterozygous CNVs and 10 heterozygous, 1 homozygous, and 1 compound-heterozygous SNVs. We validated a scoring system based on fetal and post-natal growth retardation, microcephaly and elevated IGF-I levels to identify IGF1R defect. We found a sensitivity of 92% for patients with at least 3 out of 4 criteria. In vitro, we demonstrated an impaired function of the mutated receptors. This functional test is useful to assess pathogenicity of variants of unknown significance, especially with the expansion of nextgeneration sequencing technologies. (https://jmg.bmj.com/content/early/2019/10/05/jmedgenet-2019-106328 )