Fifty seven years of follow-up of the Israeli cohort of Laron Syndrome patients-From discovery to treatment.

Clinical and laboratory investigations of dwarfed children newly Jewish immigrants from Yemen and Middle East and who resembled patients with isolated growth hormone deficiency were started by our group in 1958. In 1963 when we found that they have high serum levels of hGH, we knew that we had discovered a new disease of primary GH insensitivity. It was subsequently coined Laron Syndrome (LS, OMIM #262500). The etiopathogenesis was disclosed by 2 liver biopsies demonstrating a defect in the GH receptor. Subsequent investigations demonstrated deletions or mutations in the GHR gene. The defect lead to an inability of IGF-I generation, resulting in severe dwarfism, obesity, and other morphologic and biochemical pathologies due to IGF-I deficiency. With the biosynthesis of IGF-I in 1986, therapeutic trials started. Following closely our cohort of 69 patients with LS enabled us to study its features in untreated and IGF-I treated patients. This syndrome proved to be a unique model to investigate the effects of IGF-I dissociated from GH stimulation. In recent studies we found that homozygous patients for the GHR mutations are protected lifelong from developing malignancies, opening new directions of research.