Trisomy 21: research for a cure and rediscovery of the thought of Jérôme Lejeune

Abstract

Down syndrome (DS) is the most frequent constitutional form of intellectual disability in humans. In 1958 Jérôme Lejeune discovered that children with DS have one extra copy of chromosome 21 (trisomy 21) in their cells. Lejeune considered the trisomic cells as “drug addicted”, intoxicated by the excess of gene products that are formed due to the presence of the additional chromosome. If we knew the pathogenetic mechanisms we could devise a more specific therapy. Lejeune, a genial geneticist and biochemist, was also a pediatrician who visited thousands of children with intellectual disability, encouraging their families, highlighting the enrichment in humanity experienced by so many families because of the presence of a person with DS and not only the problems. He dedicated all of his life and so much love to these children, and at the same time he would correct the biochemical errors which hamper the full expression of their human abilities and he used to say: “Hate the disease, love the patient: that is the practice of medicine”. To date, no therapy is recognized as being effective in improving the cognitive abilities of persons with DS. Research was slowed by the fact that so many studies have been focused on prenatal diagnosis of the syndrome rather than on its treatment. Following the encounter with Lejeune’s history and work, we have started a systematic study of DS to integrate clinical, biochemical, genetic and bioinformatic data in order to identify novel therapeutic targets for this form of trisomy.