Abstract
Our objective is to present an exceptional case of a patient diagnosed with Paget's disease of the bone (PDB) while being confirmed with Lynch syndrome (LS). A 44-year-old woman was admitted for progressive pain in the left forearm 2 years ago, and was partially relieved since admission by non-steroidal anti-inflammatory drugs. Suggestive imaging findings and increased blood bone turnover markers helped the diagnosis of PDB. She was offered zoledronate 5 mg. She had two more episodes of relapse, and a decision of new medication was taken within the following years (a second dose of zoledronate, as well as denosumab 60 mg). Her family history showed PDB (mother) and colorectal cancer (father). Whole exome sequencing was performed according to the manufacturer's standard procedure (Ion AmpliSeq™ Exome RDY S5 Kit). A heterozygous pathogenic variant in the SQSTM1 gene (c.1175C>T, p.Pro392Leu) was confirmed, consistent with the diagnosis of PDB. Additionally, a heterozygous pathogenic variant of MSH2 gene (c.2634+1G>T) was associated with LS. The patient's first-degree relatives (her brother, one of her two sisters, and her only daughter) underwent specific genetic screening and found negative results, except for her daughter, who tested positive for both pathogenic variants while being clinically asymptomatic. The phenotype influence of either mutation is still an open issue. To our current knowledge, no similar case has been published before. Both genetic defects that led to the two conditions appeared highly transmissible in the patient's family. The patient might have an increased risk of osteosarcoma and chondrosarcoma, both due to PDB and LS, and a review of the literature was introduced in this particular matter. The phenotypic expression of the daughter remains uncertain and is yet to be a lifelong follow-up as the second patient harbouring this unique combination of gene anomalies.