IGF-I Deficiency: Lessons from Human Mutations

Abstract

IGF-I deficiency may be caused by defects in growth hormone (GH) secretion or action. This chapter will focus on genetic mutations causing primary defects of IGF-I synthesis or disturbance of the GH-IGF-I axis resulting in GH insensitivity (GHI). Two patients with mutations of the IGF-I gene have been described. They have several features in common: intra-uterine growth retardation (IUGR), microcephaly, mental retardation, deafness, growth failure and variable insulin resistance. Mutations of the GH receptor (GHR) or downstream signaling pathway or of peptides essential for the formation of the ternary complex also cause IGF-I deficiency, resulting in some disturbance of linear growth. The phenotypic and endocrine features of these mutations causing GHI will also be discussed.