Introduction. Down syndrome is the most common chromosomal disorder, with a worldwide frequency of 1 case in 700 live births. Objectives. Starting from the hypothesis that with the increased life expectancy of the patients with Down syndrome, new phenotypic changes and new dysfunctions are expected to appear, we proposed a longitudinal study to analyze their evolution over a long period of time. Material and method. This is a longitudinal study, based on retrospective research and descriptive evaluation, performed on a group of 81 patients from the case series of the Bihor Regional Center for Medical Genetics from Oradea. Results. We have identified 4 types of evolutionary trends of the clinical signs: stationary, involutive, progressive and with late onset. Conclusions. Knowledge of the natural evolution of the signs and symptoms of the disease is indispensable in the long-term monitoring of patients with Down syndrome. The birth of a child with Down syndrome is a real drama for the family with a strong emotional impact that can be prevented or mitigated by facilitating prenatal diagnosis, psychological counselling, social support and specialized genetic advice.