RB1 and Li-Fraumeni syndrome: The combination of constitutional mutation of the RB gene (germline retinoblastoma) and radiation therapy is linked with a particularly high risk of developing osteosarcoma, Li-Fraumeni syndrome (germline p53 mutation), and Rothmund-Thomson syndrome (autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, and cataract).