Abstract
Determination of human growth is mostly genetic (80%) and only partially environmental (20%). The key genes regulating growth include genes encoding proteohormones a related molecules (growth hormone, IGF-1, IGF-2, acid-lable subunit ALS), hormonal receptors (receptors for growth hormone, IGF and pituitary releasing hormones - GHRH and ghrelin), with a limited role of enzymes (PAPPA2).
Genes encoding transcription factors regulate pituitary morphogenesis (sonic hedgehog cascade and others) and differentiation (PROP1, POU1F1) and also chondrocytes (SHOX). Structural molecules include components of cartilagineous extracellular matrix (gens encoding aggrecan, collagens, matrillin, fibrillin and others).
The spectrum of genes responsible for both severe growth failure and minor variability of height includes genes for paracrine chondrocyte signalisation (FGFR3/NPR2 system), for intracellular signalisation (Ras-MAPK cascade, JAK-STAT signalling pathway) and for fundamental intracellular processes - regulation of DNA epigenetic modifications and control of DNA integrity. Genetic testing offers dual benefits: Immediate, as it bears an important information for the patient and his/her family about the disease nature, its future outcome and its inheritance - and a long-term - each testing contributes to understanding of disease mechanisms and to proposing novel therapies.