Down syndrome (DS) is a lifelong condition present at birth, characterized by common physical features and developmental differences. Individuals often share a distinctive appearance, which may include a flattened facial profile, upward-slanting eyes, and a single deep crease across the palm. The condition affects cognitive development, typically resulting in mild to moderate intellectual disability, and is associated with an increased risk of certain health issues. The history of understanding DS moves from simple clinical observation to a precise genetic explanation.
Early Observations of the Phenotype
The characteristic features of Down syndrome were observed long before the condition was formally named and classified. Evidence suggests individuals with this phenotype appeared throughout history, even reaching the attention of artists during the Renaissance. For example, a 16th-century Flemish painting, The Adoration of the Christ Child, is believed to depict figures with features suggestive of the syndrome, such as flattened mid-faces and upslanted eyes. Isolated medical reports also surfaced in the early 1800s, with French physicians like Jean-Étienne Dominique Esquirol and Édouard Séguin noting specific groups of individuals with intellectual disabilities who shared certain physical traits. However, these early accounts lacked the systematic classification necessary to identify the condition as a singular medical entity separate from other forms of intellectual disability.
Formal Classification and Naming
The first formal medical description establishing Down syndrome as a distinct group was published in 1866 by the British physician John Langdon Down. His paper, “Observations on an ethnic classification of idiots,” was based on his clinical examination of patients at the Earlswood Asylum for Idiots. Down grouped patients based on shared physical features, a practice influenced by 19th-century theories of racial classification and degeneration.
He focused intensely on one group of patients whose facial characteristics he erroneously believed resembled those of the Mongolian race. These features included a broad, flat face, oblique eye fissures, and a thick, fissured tongue. He labeled this group the “Mongolian type of idiocy,” a term that soon became widely adopted in the medical community as “Mongolism.”
Down’s work was purely observational; he classified the syndrome based on physical appearance and developmental characteristics, not on any understanding of its underlying cause. His theory incorrectly posited that the condition was a form of “reversion” to an earlier, supposedly “inferior” racial type.
The 1866 publication marked the first time the condition was separated from the general category of intellectual disability and recognized as a consistent clinical syndrome. The name “Down syndrome” was later adopted to honor his role as the first describer of the clinical picture, retiring the outdated racial term.
Uncovering the Biological Cause
The true scientific understanding arrived nearly a century after Down’s classification, shifting the focus from observation to genetics. The pivotal breakthrough occurred in 1959 when French geneticist Jérôme Lejeune, working with Marthe Gautier and Raymond Turpin, discovered the chromosomal anomaly responsible for the syndrome. This discovery was possible due to new laboratory techniques that allowed scientists to accurately count and visualize human chromosomes.
Lejeune and his colleagues used karyotyping, a method involving staining and photographing chromosomes during cell division to arrange them in homologous pairs. By examining cells from individuals with the syndrome, they demonstrated that the root cause was a specific genetic error, not racial degeneration or an environmental factor. They found that a person with the condition possesses 47 chromosomes in their cells instead of the usual 46.
This extra genetic material was identified as a complete or partial extra copy of chromosome number 21. The condition was scientifically named Trisomy 21, with “trisomy” referring to the presence of three copies of a chromosome instead of the normal two. This finding was monumental because it was the first time an intellectual disability in humans was definitively linked to a chromosomal abnormality.
The discovery of Trisomy 21 transformed the medical perspective, offering a clear biological etiology and ushering in the modern era of cytogenetics. This new understanding established the condition as a distinct genetic event, leading to the formal adoption of the terms “Down syndrome” and “Trisomy 21” worldwide.