TP53 and Li-Fraumeni syndrome: One consistent finding, however, is the higher incidence of osteosarcoma relative to the general population in individuals with familial Li-Fraumeni syndrome (germline TP53 inactivation), hereditary retinoblastoma (germline RB1 inactivation), Rothmund-Thomson syndrome (germline RECQL4 inactivation), or Bloom or Werner syndrome (germline BLM or WRN inactivation, resp).