Retinoblastoma is caused by changes to the RB1 tumour suppressor gene or MYCN oncogene.
Most often, these changes happen only in the retinal cell that becomes a cancer. Sometimes, they are present in every cell throughout the body, and can be passed to the next generation.
Molecular genetic testing of blood can pinpoint changes that caused tumours to form, and even when they happened.
When the RB1 gene mutation is known for the person who has retinoblastoma, genetic testing of blood relatives can determine risk to other children in the family.
Genetic knowledge is hugely valuable as testing eliminates risk of cancer in 90% of infants in families affected by retinoblastoma. Children who are found not to carry their relative’s mutations do not need routine eye exams under general anaesthetic.
However, molecular genetic testing is expensive and available at only a few places worldwide. Most families cannot access genetic testing, and struggle even to find someone who can explain the risks to them in simple terms.
Retinoblastoma genetics are complicated, especially when a child has cancer in one eye. The different scenarios and what they mean for medical care can cause great confusion and upset.
We hope this section will help you understand your child’s risks or your own more clearly, and give you some comfort and knowledge to be a confident healthcare advocate.
Heritable and non-heritable retinoblastoma both arise from changes to the RB1 gene. Errors may occur in a single cell, or in all cells throughout the body. Unilateral cancer may also arise from changes to the MYCN gene in a single cell.
About 1% of children with unilateral retinoblastoma and no family history have two normal copies of RB1. The cancer is instead caused by too many copies of the MYCN gene. Average age at diagnosis is 4.5 months, and babies typically have advanced cancer.
Mosaicism is a rare but important form or heritable retinoblastoma. Errors happen at or after conception. They are not inherited, meaning siblings are not at risk.
A genetic counselor is specially trained to help you understand risk for retinoblastoma In your family and arrange genetic testing.
Genetic testing looks for mutations in tumour from removed eyes and/or blood, and quantifies risk when a mutation is not detected.
Genetic testing results inform patient care, identify at risk family members, and eliminate risk for infants who would otherwise require frequent surveillance.
Pre-implantation Genetic Diagnosis (PGD)
When a person has a heritable RB1 mutation, Pre-implantation Genetic Diagnosis can be used with In Vitro Fertilization (IVF) to avoid passing the genetic mutation to the children.
Simple explanation of genetics terminology.