Spotted bones in an osteopoikilosis-related disease (Buschke Ollendorff Syndrome): Identifying this rare condition from the lab to the field.

Objective: To improve the differential diagnosis of osteopoikilosis in past populations using a clinical case as an example of this rare condition.

Materials: A patient referred to our Genetic Service with suspected Buschke Ollendorff Syndrome after finding a connective nevus.

Methods: Radiological images from different body regions were accompanied by a genetic study using next-generation sequencing.

Results: Small circular-to-ellipsoid sclerotic lesions were found in the epiphysis and metaphysis of long bones, as well as in the pelvis. These lesions were bilaterally distributed and with well-defined margins, compatible with the characteristics of Buschke Ollendorff Syndrome, bone manifestation osteopoikilosis. A heterozygous mutation on LEMD3 (NM_001167614:c.1918 + 1G > C) was identified by next-generation sequencing. Based on this confirmed case, we have discussed the most probable causes of similar bone lesions found in the archaeological record.

Conclusion: It has been demonstrated how a current case of a rare disease can provide useful tools to improve the differential diagnosis of this disease in ancient skeletons.

Significance: This work underlines the great need for multidisciplinary platforms that integrates clinical research into paleopathology in order to successfully address the study of rare diseases from the past.

Limitations: Since OPK is only detected by X-rays, suspected cases of this bone lesion will only be identified when radiographs are taken for other purposes.

Suggestions For Further Research: Retrospective and large-scale studies of radiographs from other research in past populations.