More than 30 million people in Europe live with a rare disease today. Although rare diseases are often perceived as modern medical challenges, scientific research now confirms that they have affected humans for thousands of years.
This long history is illustrated by a recent study published in The New England Journal of Medicine, co-authored by Adrian F. Daly, Internist-Endocrinologist and Researcher at the CHU de Liège, Liège University, Belgium and Endo-ERN expert. The study reports the genetic diagnosis of a rare disease affecting growth in a family who lived more than 12,000 years ago, using advanced ancient DNA analysis. It is the earliest genetic diagnosis ever made in humans.
The researchers identified a pathogenic variant in the NPR2 gene in prehistoric human remains excavated from the Romito Cave in southern Italy. This variant, when two copies are present, causes acromesomelic dysplasia, Maroteaux type (AMDM) (ORPHAcode: 933), an ultra-rare skeletal dysplasia characterised by severe disproportionate short stature and functional limitations. The genetic findings closely matched the skeletal features observed, demonstrating how genomic analysis can confirm diagnoses that would otherwise remain speculative — even across millennia. “What is striking is that we can now apply modern genomic tools to conditions that clearly affected people thousands of years ago,” says Adrian F. Daly. “The same principles that allow us to make sense of ancient cases are central to improving diagnosis and care for patients with rare endocrine disorders today.”
This discovery reinforces the importance of genomic testing in rare disease care. Accurate molecular diagnosis is essential for reducing diagnostic delays, supporting clinical decision-making, informing patients and families, and enabling access to appropriate expertise and research.
For people living with rare endocrine conditions today, access to specialised knowledge and coordinated care remains a challenge. Endo-ERN works to address this by connecting healthcare professionals across Europe, facilitating expert consultation, supporting the development of clinical guidance, and improving access to high-quality care regardless of where patients live.
By linking modern genomic medicine with coordinated expert networks, Europe is strengthening its capacity to support people living with rare diseases — conditions that have been part of the human story for millennia.
Read the full article and supplementary appendix.
Fernandes DM, Llanos-Lizcano A, Brück F, Oberreiter V, Özdoğan KT, Cheronet O, Lucci M, Beckers A, Pétrossians P, Coppa A, Pinhasi R, Daly AF. A 12,000-Year-Old Case of NPR2-Related Acromesomelic Dysplasia. N Engl J Med. 2026 Jan 29;394(5):513-515. doi: 10.1056/NEJMc2513616. PMID: 41604646.
