Deletion of both Rb (retinoblastoma) genes in the same developing cell is most characteristically associated with the development of

Retinoblastoma is the most common malignant tumor of the eye in children. Clinically, retinoblastoma may produce a white pupil (leukocoria). This is seen most often in young children in the familial form of retinoblastoma, which is due to a deletion involving chromosome 13. These familial cases of retinoblastoma are frequently multiple and bilateral, although like all the sporadic, nonheritable tumors they can also be unifocal and unilateral. Histologically, rosettes of various types are frequent (similar to neuroblastoma and medulloblastoma). There is a good prognosis with early detection and treatment; spontaneous regression can occur but is rare. Retinoblastoma belongs to a group of cancers (osteosarcoma, Wilms tumor, meningioma, rhabdomyosarcoma, uveal melanoma) in which the normal cancer suppressor gene (antioncogene) is inactivated or lost, with resultant malignant change. Retinoblastoma and osteosarcoma arise after the loss of the same genetic locus--hereditary mutation in the q14 band of chromosome 13. In contrast, a blue sclera can be seen with osteogenesis imperfect, while a yellow sclera is seen with jaundice. Lack of an iris (aniridia) can sometimes be associated with Wilms tumor of the kidney, while a subluxated lens can be found in individuals with either Marfan's syndrome or homocystinuria.