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.
Copyright © 2012 S. Karger AG, Basel.