++
Retinoblastoma (RB) is the most common primary intraocular malignancy
of childhood. Incidence rates vary from 1 in 14,000 to 1 in 22,000
live births, and it is estimated that 300 children develop retinoblastoma
in the United States annually.1 There is no race
or gender predilection. Approximately 80% of children are
diagnosed before the age of 3 years. More than half of patients
diagnosed in the first year of life have bilateral disease compared with
less than 10% of older children.
++
Retinoblastoma occurs sporadically in the majority
of affected children. Of all cases, approximately 60% are
unilateral and 25% are bilateral.2 All
bilateral cases and 15% of unilateral cases are hereditary.
Only 10% to 20% of hereditary cases have an affected
parent; therefore, unilateral cases without an affected parent can
be determined to be hereditary only with mutation analysis (Fig. 461-1).
++
++
Retinoblastoma (RB) appears to develop only when both alleles
of a tumor suppresser gene (RB1) located on 13q14
are absent or defective. In hereditary RB every cell in the body
inherits one absent or defective gene. During normal development,
a mutagenic “hit” to the remaining normal allele
results in the loss of normal cellular growth regulation and tumor
development.2 In sporadic, nonhereditary RB, a
single retinal cell must receive 2 mutagenic hits to the 13q14 tumor
suppressor gene before RB can be expressed. Point mutations of the RB1 gene
are the most common events. Variable deletions of the long arm of
chromosome 13 are not commonly found in patients with RB and patients
who are developmentally delayed should not be presumed to have the
chromosome 13q deletion syndrome.3,4
++
Genetic counseling for patients with retinoblastoma and their
families is complex, but a few generalizations can be made. Patients
with the hereditary form are at risk for other cancers later in
life, including soft tissue and bone sarcomas and melanoma. This
risk is increased in patients treated with radiation therapy.5 A
survivor of hereditary retinoblastoma has a 50% chance
of transmitting the gene to his or her offspring. In patients with
unilateral disease, the overall risk of transmitting the gene to
offspring is estimated to be 2.5%. With no previous family
history, the risk for a sibling is 2% if the affected child
has bilateral disease and 1% if the affected child has
unilateral disease.6 These empiric risk estimates
are based on the possibility of gonadal mosaicism. In addition,
it is estimated that 10% of individuals who carry an abnormal RB1 gene
do not develop retinoblastoma because the second event did not occur
in any cell; however, they are still at risk to develop other cancers
during their lifetime.
++
Retinoblastoma arises from the inner layer of ...