SNP Shot: Genomic Insights

Paget's disease of bone is a condition where bones grow abnormally large and weak. This can lead to bone deformities and an increased risk of fractures.

The typical form of Paget's disease usually appears in middle-aged or older individuals. It generally affects only a few bones and doesn't spread. While any bone can be affected, it's most common in the spine, pelvis, skull, or legs.

Many people with the classic form of Paget's disease have no noticeable symptoms related to the bone changes. It's often discovered incidentally during X-rays or lab tests performed for other reasons. If symptoms do develop, pain is the most common. The affected bones themselves may be painful, or the pain could be due to arthritis in nearby joints. The bone distortion, especially in weight-bearing bones like those in the legs, can cause increased wear and tear on joints, leading to arthritis. This arthritis frequently affects the knees and hips.

Other complications of Paget's disease depend on the location of the affected bones. Skull involvement can result in an enlarged head, hearing loss, headaches, and dizziness. If the spine is affected, it can cause numbness and tingling (due to nerve compression) and spinal curvature abnormalities. In the leg bones, the disease can lead to bowed legs and difficulty with walking.

Osteosarcoma, a rare type of bone cancer, has been linked to Paget's disease of bone, but it's uncommon, affecting probably less than 1 in 1,000 individuals with Paget's.

Early-onset Paget's disease is a rarer form that appears in the teens or twenties. It shares features with the classic form but is more likely to affect the skull, spine, ribs (axial skeleton), and small bones of the hands. This form is also associated with early hearing loss.

Inheritance:

In 15 to 40 percent of classic Paget's disease cases, the condition follows an autosomal dominant inheritance pattern. This means that only one copy of a mutated gene is needed in each cell to cause the disease. In the remaining cases of classic Paget's disease, the inheritance pattern isn't clear. Many affected individuals have no family history, although it sometimes clusters within families. Studies suggest that close relatives of those with classic Paget's are 7 to 10 times more likely to develop the disease compared to those without an affected relative.

Early-onset Paget's disease is also inherited in an autosomal dominant manner. Individuals with this form of the disorder need only one altered copy of the TNFRSF11A gene in each cell to develop the disease.