A 1000-year-old case of Klinefelter’s syndrome diagnosed by integrating morphology, osteology, and genetics

An international team of researchers led by the University of Coimbra (UC) has identified one of the oldest cases of Klinefelter's syndrome, a genetic syndrome in which men have an extra copy of the X chromosome. Those affected can suffer from osteoporosis, obesity and gynaecomastia, as well as being tall and having enlarged hip diameter. The individual in question lived about a thousand years ago in Castro de Avelãs, Bragança, during the Middle Ages. The discovery provides insight into the incidence of Klinefelter's in ancestors and opens up the possibility of studying the frequency of this and other genetic syndromes in the past through the analysis of human fossils.

The study “A 1000-year-old case of Klinefelter’s syndrome diagnosed by integrating morphology, osteology, and genetics”, now published in the prestigious journal The Lancet, was coordinated by CEIS20 researcher João C. Teixeira, a human genetics researcher currently working at the Australia National University. Specialists in genetics, statistics, archaeology and anthropology took part in the study, namely researchers from the Centre for Interdisciplinary Studies of the University of Coimbra (CEIS20), the Faculty of Arts of the UC (FLUC) and the Centre for Research in Anthropology and Health (CIAS) of the Faculty of Science and Technology of the University of Coimbra (FCTUC). This contact between different fields of knowledge reveals “the enormous potential of dialogue between different disciplines that complement each other in the study of the past,” says the study’s coordinator.

In addition to this discovery, the research team has also developed a new statistical method that could, in the future, “allow the diagnosis of other chromosomal anomalies, such as Down’s syndrome, and could also be used in forensic and prenatal diagnostics”, says João C. Teixeira.

In the first phase of the research, the team obtained DNA from an 11th-century skeleton found in Castro de Avelãs in 2012 by the archaeological team coordinated by CEIS20 researcher Pedro C. Carvalho, also a professor at the Faculty of Arts of the University of Coimbra. According to the researcher, “this place is of great historical importance, as it was probably the capital of the Zoelas, a people mentioned by Pliny (a Roman author from the 1st century), and the seat of the Swabian parish of Brigantia, from which the current town of Bragança This was followed by the recovery of the individual's DNA, which took place in the specialised laboratory of the Australian Centre for Ancient DNA (at the University of Adelaide, Australia). In this process of analysing ancient DNA, one of the routine objectives is to “determine the genetic sex of individuals through computer analyses that map the DNA fragments obtained on the X and Y chromosomes of the human genome”, explains Xavier Roca-Rada, doctoral student and first author of the study. The results suggested that the individual from Castro de Avelãs had two copies of the X chromosome and one of the Y chromosomes, indicative of Klinefelter’s syndrome.

After confirming the genetic results, a team of anthropologists from the University of Coimbra found morphological features in the skeleton that were consistent with Klinefelter’s, in particular “tall stature and an enlarged hip diameter,” says Sofia Tereso, an anthropologist at the UC. On the other hand, the team found no evidence of osteoporosis, which affects around 40 per cent of people with Klinefelter’s syndrome.