Genetic disorders in the growth hormone-IGF-I axis

Abstract

Growth is a complex process, regulated by multiple external and internal factors. Deviation from the normal growth pattern can be one of the first manifestations of an underlying disorder, disrupting the normal growth process. The growth hormone __ IGF-I axis plays a key role in regulating this growth process. This thesis focuses on growth disorders as a result of genetic defects in the GH-IGF-I axis. The aim of the thesis is to study the genotype-fenotype relationship in patients with a documented genetic defect in one of the components of the GH-IGF-I axis and to unravel the role of the GH-IGF-I axis in the complex process of growth and development throughout life. Two patients with a mutation in the GH releasing hormone receptor gene demonstrate that combined treatment of GH and gonadotropin-releasing hormone antagonists is very effective in increasing final height. The characteristics of the first male patient with a STAT5b mutation are described in detail. The fenotype of the first patient with an inactivating mutation of the IGF-I gene is described, as well as functional characteristics of the mutation. Finally the consequences of a genetic defect of the IGF-I receptor gene are discussed.