Intrauterine Growth Retardation and Postnatal Growth Failure Associated with Deletion of the Insulin-Like Growth Factor I Gene

Abstract

Insulin-like growth factor I (IGF-I) mediates the majority of the growth-promoting effects of growth hormone (GH) after birth.1 In the prenatal period, GH does not appear to have a major influence on fetal growth, whereas IGF-I does. Infants with congenital GH deficiency and defects in the GH-receptor gene have only mild retardation of growth at birth,2-4 whereas transgenic mice with a homozygous defect of the IGF-I gene (IGF-I knockout mice) have profound embryonic and postnatal growth retardation.5-7 Although there is no direct evidence that IGF-I has a prominent role in human fetal growth, fetal tissues express IGF-I from an early stage, and fetal and cord serum IGF-I concentrations are correlated with fetal size.8-11 IGF-I knockout mice also have defects in neurologic development, indicating that IGF-I may have specific roles in axonal growth and myelination.12 In addition, neonatal mortality is substantial, suggesting that this defect may be lethal in humans. In this report, we describe a 15-year-old boy with severe prenatal and postnatal growth failure, sensorineural deafness, and mental retardation who had a homozygous partial deletion of the IGF-I gene.