Abstract

Despite the fact that a specific cause is not determined in children with idiopathic short stature, there is, at least hypothetically, an as yet undetermined pathophysiological process present. The full spectrum of clini-cal and laboratory signs, from relative growth hormone deficiency to resistance, can be present in these children. Several possible causes have been determined in the growth hormone-IGF1 axis. Genetic muta-tions in the growth hormone receptor gene, in genes involved in the intracellular growth hormone receptor signalling pathway, the growth factor IGF-1 gene or the acid-labile subunit gene that forms a ternary struc-ture together with IGF-1 and its binding protein IGFBP-3 and in this way prolongs the IGF-1 circulating half-life, have been determined. In addition, mechanisms not associated with the growth hormone-IGF-1 axis have been determined: mutations in the SHOX gene, genes involved in DNA transcription, genes encoding proteins of the MAPK signalling pathway, and genes involved in the timing of the growth and development of the whole body and specifically, the growth plate. In addition to genetic causes, epigenetic causes have an important effect on height and will, in the future, help us better understand the variability in height in the general population. Categorising the causes of short stature is of importance from the point of view of the effectiveness and safety of growth hormone therapy. In the future, the long-term safety and economic and psychosocial efficacy of treatment of idiopathic short stature in children need to be more clearly defined.

Key words: short stature, child, adolescent, growth hormone, IGF-1, IGFBP-3, ALS, SHOX.