Role of Insulin- Like Growth Factors in Growth, Development and Feeding

Information about the role of insulin- like growth factors (IGFs) is mainly derived from knockout (KO) and transgenic mice, human mutations in IGF1, IGF1R and IGFALS, and association studies with IGF1 SNPs. Igf1 KO mice show severely impaired pre- and postnatal growth and brain development and sensori-neural hearing loss. Both local and endocrine IGF- 1 are needed for normal growth. Igfals KO mice show a modest postnatal growth attenuation. Homozygous igf1r KO mice are severely growth impaired, while heterozygous mutations only show mild growth retardation. Two patients with a complete absence of biologically active IGF- 1 showed severe pre- and postnatal growth, extreme microcephaly, sensorineural deafness and failure to thrive. A patient with a mutation that led to a partially functional protein had a less severe growth phenotype and no deafness, similarly to two siblings with a heterozy-gous IGF1 mutation. Heterozygosity for a dysfunctional IGF1 mutation leads to a mild effect on birth weight, adult height and head circumference. Patients with heterozygous mutations or deletions of IGF1R have a moderate pre- and postnatal growth failure, microcephaly and a history of feeding prob-lems. Children with homozygous mutations of IGFALS have a low or normal birth weight, a mild growth failure, a head circumference in the lower normal range, and no failure to thrive. Association studies o