50 Years Ago in The Journal of Pediatrics:

Article Outline

• Copyright

Warkany J. J Pediatr 1960;56:412-9

Although Down syndrome had been described by John Down in 1866, it took almost 100 years until the cause of this disorder was identified, leading to a “Conference on the Etiology of Mongolism” held on October 19, 1959. Only 3 years before, it was determined that the actual number of human chromosomes was 46. This exciting new discovery led to identifying the cause of numerous syndromes, including Down syndrome (trisomy 21), the most common chromosome disorders. The field of genetics and birth defects has significantly progressed since this publication, and it is likely that the authors did not foresee the sequencing of the entire human genome, including identification of all the genes on chromosome 21.

Down syndrome became a model for understanding the epidemiology of numerous genetic conditions. Research in Down syndrome has led to greater insight into many associated maladies, including developmental disabilities, congenital heart malformations, leukemia, Alzheimer's disease, and autism spectrum disorders. Because of the support and curiosity of these pioneers, clinics and centers devoted to the management of individuals with Down syndrome were established and serve as resources for research into the causes of Down syndrome and other chromosome disorders, identification and treatment of associated complications and initiating developmental and educational interventions, which serve as the cornerstone of how our communities approach all children and adults with developmental disabilities.

The committee concluded that discovery of a chromosomal abnormality in Down syndrome will change the direction of etiologic research in this area and “will stimulate the development of many new approaches toward the understanding of this disease.” New technologies, such as fluorescence in situ hybridization and microarray chips have led to the discovery and understanding the causes of hundreds of new disorders, opening entirely new avenues of investigation. Nonetheless, as in 1959, there remain unanswered questions, including the specific factors that cause chromosome nondisjunction, why some individuals are at higher risk for having a pregnancy with chromosome anomalies, and why two children and the exact same karyotype can have such discordant phenotypes. The next 50 years should bring answers to these and many other related questions and undoubtedly will raise many new questions.