In 1877, Sir James Paget first described the localized skeletal disease that is now known as Paget’s disease of the bone (PDB)(1). The disease is primarily a disorder of the osteoclast with marked increase in bone resorption, followed by abundant new bone formation. In this report, we present a brief overview of the genetics of PDB; a complete review was recently published by Singer and Leach (2). PDB has a familial tendency (3–5), suggesting that there is a genetic predisposition. In a study of the frequency and characteristics of the familial aggregation of PDB in Spain, Morales-Piga et al.(6) found that 40% of their index cases had at least one first-degree relative affected with PDB. In the pedigrees they reported, PDB seemed to be transmitted through either parent, suggesting an autosomal dominant mode of inheritance.

Siris (7) conducted an epidemiological study of PDB in the United States, using questionnaires completed by 864 patients with physician-diagnosed PDB, and compared these results to 500 controls of similar age. A history of PDB was noted in a first-degree relative in 12% of the patients, compared with only 2% of controls. The risk of first-degree relatives of a pagetic patient developing PDB was seven times greater than for an individual without an affected relative. The cumulative risk for developing PDB up to age 90 for a first-degree relative of a patient was 9% compared with 2% in individuals with unaffected relatives. This is good evidence that a gene, or genes, plays a role in the acquisition of the disease.