title: Downstream insulin-like growth factor.
abstract: Until 10 years ago genetic defects that cause a child to be born small for gestational age (SGA) were poorly defined. With the first descriptions of patients born small for gestational age carrying mutations within the insulin-like growth factor type 1 receptor (IGF-1R) gene, genetic defects at the lower end of the GH-IGF-1 axis were identified as a monogenetic cause of intrauterine growth retardation. These patients failed to thrive despite normal IGF-1 serum concentrations thereby establishing a concept of IGF-1 resistance in these patients. The identification of additional patients along with functional, genetic and structural examinations of the different IGF-1R mutations have provided evidence for a variability of the pathogenic impact that mutations of the IGF-1R have on human longitudinal growth. However, the seemingly variable incidence of further clinical features such as developmental delay, suggest that at least some of the functions within the IGF-IGF-1R system are in part redundant. This redundancy may depend on the genetic background and environmental factors. At the lower end of the GHRH-IGF-1 axis, primary IGF-1 deficiency and IGF-1 resistance due to defects within the IGF-1 and IGF-1 receptor (IGF-1R) genes account for approximately 10-15% of all cases with intrauterine and postnatal growth retardation.
authors.affiliation: Department of Pediatrics, University of Leipzig Medical School, Leipzig, Germany. rpfaeffle@medizin.uni- leipzig.de
authors.forename: Roland
authors.initials: R
authors.lastname: Pfäffle
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
mesh_terms: D000818:Animals; D002648:Child; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000209:etiology / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood / Q000254:growth & development; D008954:Models, Biological; D011247:Pregnancy; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013002:Somatomedins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D013002:Somatomedins; D017526:Receptor, IGF Type 1