A new study published in the New England Journal of Medicine reports the oldest case of genetic disease diagnosed through DNA in an individual who lived over 12,000 years ago. This discovery demonstrates how tools developed for modern clinical genetics can redefine our understanding of rare diseases in prehistory, creating a bridge between medicine, genomics and archaeology.

The research focuses on an extraordinary Upper Palaeolithic burial discovered in 1963 inside the Romito Cave, a cave site in Calabria, southern Italy, where two individuals were laid to rest together, locked in an embrace. One is an adult male (Romito 1) shorter than the average height for people of that era (145 cm), and the other is an adolescent male (Romito 2) characterised by markedly shortened limbs and extremely reduced stature (110 cm).  For decades, some fundamental questions remained unanswered regarding the sex of the two individuals, the reason why they were buried together, and the reason for their short stature, especially that of the smaller individual. Examination of the bones suggested the presence of a rare skeletal disorder called acromesomelic dysplasia. However, this diagnosis had never been confirmed.

To answer these questions, an international and multidisciplinary team comprising researchers from the Department of History, Anthropology, Religions, Art and Performing Arts at Sapienza University, the Department of Evolutionary Anthropology at the University of Vienna, the University Hospital Centre in Liège and the Centre for Anthropology and Health (CIAS) at the University of Coimbra, extracted DNA from the inner ear, one of the most reliable sources in ancient skeletons. Genetic analysis first clarified that both individuals were female and that they were first-degree relatives, most likely mother and daughter.

Furthermore, in Romito 2 (the adolescent), a homozygous variant (two copies) of the NPR2 gene was identified, confirming the diagnosis of Maroteaux-type acromesomelic dysplasia, a rare hereditary genetic disorder that causes severe growth reduction and marked limb shortening. The results of the analyses on Romito 1 (the mother) suggest that she was a carrier of only one altered copy of the NPR2 gene, which causes only below-average height. What was observed in these Upper Palaeolithic individuals is perfectly consistent with the clinical characteristics of modern patients with one or two abnormal copies of the NPR2 gene.

The study demonstrated that the science of ancient DNA analysis, or palaeogenomics, is capable of confirming specific genetic mutations, providing not only a minimum reliable date for certain rare conditions, but also revealing previously unknown variants.

From a medical perspective, the findings shed new light on the topic of rare diseases in human history. Rare genetic diseases are not a modern phenomenon, but have always been present in humans. Genomic analyses of ancient DNA can identify many other rare genetic diseases, including several that have remained hidden until now.

Finally, this discovery conveys a powerful human message: Romito 2 survived into late adolescence, suggesting the existence of ongoing social care in a hunter-gatherer community over twelve thousand years ago. ‘We assume that her companions took good care of her, helping her to find food and supporting her mobility during periodic movements in a harsh and challenging environment,’ says Alfredo Coppa of Sapienza University, co-director of the study.

References: Daniel M. Fernandes, Alejandro Llanos-Lizcano, Florian Brück, Victoria Oberreiter, Kadir Özdoğan, Olivia Cheronet, Michaela Lucci, Albert Beckers, Patrick Pétrossians, Alfredo Coppa^*, Ron Pinhasi^*, Adrian F. Daly^* (* made equal contributions) A 12,000-Year-Old Case of NPR2-Related Acromesomelic Dysplasia. New England Journal of Medicine, 2026, 394;5: 513-516 (DOI: 10.1056/NEJMc2513616).

Further Information

Michaela Lucci – Department of Environmental Biology

michaela.lucci@uniroma1.it

Alfredo Coppa – Department of History, Anthropology, Religions, Art and Performing Arts (SARAS)

alfredo.coppa@uniroma1.it