Retinoblastoma genetic testing is valuable for affected children, adult survivors and unaffected relatives.
Results inform patient care, identify at risk family members, and eliminate risk for infants who would otherwise require frequent eye surveillance under general anaesthetic.
Genetic testing is 75% cheaper than conventional screening for unaffected children and children with unilateral retinoblastoma.
What Genetic Test Results Mean
A constitutional RB1 mutation IS found in the proband (person with retinoblastoma).
High risk to the unaffected eye is confirmed when the child has unilateral cancer. The child also has a lifelong risk for other cancers, and should avoid radiation exposure wherever possible.
The proband’s children have a 50/50 risk of inheriting the mutation. Dilated eye exams, including EUA, are recommended from birth, until genetic testing of the infant eliminates risk.
Testing of blood relatives can identify their risk. If testing of an unaffected sibling finds no mutation, they and their offspring have no greater risk than the general population. Unaffected children do not require surveillance exams.
If a mutation is not detected in the proband’s parents, one parent may have an undetectable mosaic mutation. If more than one child in the family has retinoblastoma, one parent will definitely have an RB1 mutation, even if it is not detected. A parent with an undetected mosaic mutation has an increased lifetime risk of other cancers.
When a parent has a mosaic mutation, their children are at risk of inheriting the mutation, which will be present in every cell. Risk may be lower than 50/50, depending on the degree of mosaicism. Dilated eye exams, including EUA, are recommended from birth, until genetic testing of the infant eliminates risk.
A mosaic RB1 mutation is found in the proband
High risk to the unaffected eye is confirmed when the child has unilateral cancer. Risk may be relative to the percentage of mosaic cells.
The child also has a lifelong risk for other cancers, and should avoid radiation exposure wherever possible.
The proband’s children are at risk of inheriting the mutation, which will be present in every cell. Risk may be lower than 50/50, depending on the degree of mosaicism. Dilated eye exams, including EUA, are recommended from birth, until genetic testing of the infant eliminates risk.
Mosaicism cannot be inherited. Parents and siblings do not require genetic testing, and siblings do not require surveillance exams.
A constitutional RB1 mutation is NOT found in blood of a bilateral or trilateral proband
All children with bilateral and trilateral retinoblastoma have a constitutional RB1 mutation. If mutations are found in tumour but not in blood, the child has a mosaic mutation in such a low fraction of cells that current technologies cannot find it.
The proband’s children are at risk of inheriting the mutation, which will be present in every cell. Risk may be lower than 50/50, depending on the degree of mosaicism. Dilated eye exams, including EUA, are recommended from birth, until genetic testing of the infant eliminates risk.
Mosaicism cannot be inherited. Parents and siblings do not require genetic testing, and siblings do not require surveillance exams.
A constitutional RB1 mutation is NOT found in tumour of a bilateral or trilateral proband
All children with bilateral and trilateral retinoblastoma have a constitutional RB1 mutation. In the rare instance that no mutation is found in tumour, there remains a 10% risk that one parent also carries an undetected RB1 mutation. Therefore, the proband’s siblings each have a 5% risk to inherit the mutation.
Parents and siblings cannot receive genetic testing when the proband’s mutation is unknown. Dilated eye exams, including EUA, are recommended for siblings from birth until 6 years old.
The proband’s children have a 50/50 risk of inheriting the mutation. Dilated eye exams, including EUA, are recommended from birth until 6 years old.
Genetic testing for retinoblastoma is continually advancing, and subsequent testing may identify the proband’s RB1 mutation. Staying in contact with the testing lab and genetic counselor will be valuable.
An RB1 mutation is found in tumour but NOT in blood of a unilateral proband with no family history; or tumour testing is not possible and mutation is NOT found in blood.
The child may have a mosaic mutation in such a small percentage of cells that it cannot be detected with current molecular technologies. If the lab is capable of precise testing for mosaicism, the child’s risk is reduced from 17% to less than 1%.
This result can dramatically impact the child’s care. Office exams can replace EUAs much sooner. The risks posed by anaesthesia far outweigh the tiny chance of finding a tumour in the unaffected eye.
Mosaicism cannot be inherited. Parents and siblings do not require genetic testing, and siblings do not require surveillance eye exams.
The proband’s children have a 0.5% risk of inheriting an RB1 mutation, which will be present in every cell. If mutations are identified in the parent’s tumour, genetic testing can look for them in the infant’s blood. Dilated eye exams are advised from birth, until genetic testing of the infant eliminates risk.
Both copies of RB1 in tumour are normal and amplification of MYCN is found in a child with unilateral cancer and no family history.
The child has RB1+/+MYCNA retinoblastoma, which is non-hertiable. This means office exams can replace EUAs much sooner as there is no risk to the healthy eye.
This type of retinoblastoma is not inherited. Parents, siblings and offspring do not require genetic testing, and infant siblings and offspring do not require surveillance eye exams.
