IGF1R mutations as cause of SGA.
Until 2003 monogenetic aberrations that lead to a child that is born too small for gestational age (SGA) were poorly defined. With the first report of mutations within the insulin-like growth factor type 1 receptor (IGF1R) gene in two non-syndromic patients born SGA, who failed to thrive despite normal or even elevated IGF1 serum concentrations the concept of IGF1 resistance has been established. The identification of additional individuals bearing IGF1R mutations along with comparative, genetic, structural and biochemical studies has provided evidence for the pathogenic impact of the IGF1R mutations on human longitudinal growth. However, the variability in the occurrence of additional clinical manifestations, such as developmental delay, might indicate that the pleiotropic functions of the IGF-IGF1R system are partially redundant. It is apparent that we have just begun to unravel the multifaceted IGF1R actions at the interface of growth control, maintenance of metabolic homeostasis and neurodevelopment and neural protection.