The incidence delete of retinoblastoma is 1 per 15,000–30,000 live births. In one-third of cases, retinoblastoma occurs in both eyes and is conside red hereditary. These forms occur usually at a lower age compared to sporadic cases. Unilateral forms are usually not hereditary and is usually diagnosed around the age 2 years.

Hereditary forms are typically bilateral or multifocal and are usually diagnosed much earlier, even in the first year of life. Transmission is autosomal dominant with a high risk of occurrence in the siblings and offspring. The risk of transmission to children is 50 %. In 15–20 % of unilateral forms there are mutations in germ cells, with a risk of transmission to the offspring of 50 %.

According to Knudson’s theory, two genetic lesions are necessary for the occurrence of retinoblastoma. The first mutation is inherited at the level of the germ cells, while the second mutation occurs spontaneously at the level of the somatic retinal cells and other body tissues. In both mutations, somatic retinal cells are involved in the nonhereditary form. This hypothesis explains the significant higher risk of second cancers in the hereditary forms.

The retinoblastoma gene has been identified and cloned as a tumor suppressor gene located at 13q14 chromosome. The loss of both alleles is required for oncogenesis process of retinoblastoma. Deletion shown in the karyotype, but more often a point mutation leads to mRNA incomplete or absent transcript of retinoblastoma gene. In 5 % of cases, there is an association with other abnormalities and particularly those related to a deletion of chromosome 13 (Table 10.1).

Retinoblastoma seems more frequent in Africa representing the second or third most frequently seen tumor in some pediatric cancer u nits. No particular predisposing factor has been demonstrated in this setting so far.

Most tumors have an endophytic development (toward vitreous) and exophytic (toward subretinal space). Exophytic extension can cause a retinal detachment. Glaucoma can also occur following occlusion of the trabecular neovascularization network, Iris or invasion to the optic nerve.

If extraocular extension is present, it can reach the orbit or optic nerve; the tumor can also reach preauricular or maxillary lymph nodes through lymphatic pathway, and via the bloodstream of the brain, bones, bone marrow, and other organs. Retinoblastoma can invade the optic nerve and extend along the axons to the brain or across the subarachnoid space and extend to the brain or cerebrospinal fluid. The presence of anorexia, vomiting, headache, or weight loss is usually a manifestation of cerebrospinal metastases.

In the trilateral retinoblastoma, there is an intracranial median most often with pineal involvement, which is associated with the bilateral form. Evolution towards spinal metastases is frequent and has a poor prognosis.

In developed countrie s, the tumor is mostly diagnosed as intraocular retinoblastoma, while in developing countries, most patients attend hospital long after the cancer has spread beyond the eye and extraocular disease is present.

The most common symptoms of retinoblastoma in developed countries are leukocoria and strabismus. Leukocoria is a white reflection of the pupil (derived from Greek leukos meaning “white” and “kore” meaning “pupil”). Leukocoria is an early sign of retinoblastoma, but unfortunately irregular, and is sometimes noticed only after a photoflash. Strabismus is also frequently noted in the early stages.