Retinoblastoma is a malignant tumor of the eye that originates
in developing retinal cells. Conventional care for retinoblastoma
families calls for repeated retinal examinations for each first-degree
infant relative until the age of 7 years. For infants less than
3 years of age, examinations are often performed in an operating
room while the patient is anesthetized.
Only 10% of patients with retinoblastoma have a positive family
history. Ninety percent of infants at risk do not carry the mutation
that causes the disease, but carrier status cannot be assessed without
genetic testing. Conventional care for retinoblastoma families is
not only invasive and costly, but for many individuals, unnecessary
if molecular testing is available.
A necessary precursor to retinoblastoma is occurrence of a mutation
in each allele of the RB1 gene of cell(s) that grow to be
tumors. Most affected families carry an RB1 mutation unique
to that particular family. The RB1 gene mutation can be determined
by molecular analysis with 90% test sensitivity. Once a family's
mutation is identified, blood from family members can be tested
immediately. In this way, most infants at risk (90%) are shown not
to need surveillance at all. The infants who carry a familial mutation
(10%) are also identified, who require intensive clinical surveillance
to detect and treat tiny retinoblastoma tumors before they damage
vision.
Research (Richter et al, Amer J Hum Gen, 2003) shows that when
conventional care is augmented by systematic, optimized genetic
testing, the quality of care improves and the average cost per family
declines. Cost savings occur because of substantial reduction in
diagnostic uncertainty and elimination of many unnecessary clinical
examinations, since only 10% of relatives at risk actually carry
the mutation.
