A case of sclerosing bone dysplasia from 16th century Sardinia: Camurati-Engelmann disease?

The skeletal remains of a male aged 45-55 years displaying several bone anomalies were unearthed from the Alghero plague cemetery “lo Quarter”, a burial site dating back to the 1582-1583 AD outbreak. The skeleton is characterised by marked thickening of the cranial vault and a symmetrical enlargement of the diaphyses of the long bones of the upper and lower limbs. The metaphyses appear to be involved, while the epiphyses are spared. X-rays and Computed Tomography showed increased irregular cortical thickness and narrowing of the medullary cavity. The individual was affected by a sclerosing bone dysplasia, a genetic disease characterised by increased bone density. Sclerosing bone dysplasias are rare genetic diseases whose variety makes the clinical diagnosis challenging; in our case the mature age of the individual, with evident signs of late stage of the disease, helped us identifying the disorder. Differential diagnosis allowed to suggest a possible case of Camurati-Engelmann disease, also known as progressive diaphyseal dysplasia. It is an autosomal-dominant condition caused by mutations within the transforming growth factor-β1 (TGFβ1) gene on chromosome 19q13, characterized by anomalies in intramembranous bone formation. It is a very rare disorder, and approximately 200 cases have been reported in the modern clinical English literature. The individual from Alghero should be symptomatic, since he is likely to have experienced the most common clinical symptoms, such as pain in the limbs and fatigability, and to have had an unusual gait. The case from Alghero represents the unique paleopathological evidence of Camurati-Engelmann disease so far diagnosed.