The molecular basis of idiopathic short stature

Forty years ago, when growth hormone (GH) first became available for use, the molecular basis for growth hormone deficiency (GHD) was entirely unknown. Despite continued difficulties with the biochemical diagnosis of GHD, we now accept the existence of underlying genetic abnormalities as the basis for disorders involving GH secretion. Similar challenges are encountered when one considers the causes of non-GHD short stature, namely idiopathic short stature (ISS). Categorization of the causes for ISS by insulin-like growth factor I (IGF-I) concentrations provides a basis for speculation about the potential for IGF-I gene polymorphisms or binding protein abnormalities influencing the development of ISS-related growth failure.