"Retinoblastoma Predisposition" – What Is It?
Retinoblastoma is a malignant tumor of the immature retina of the eye that is caused by mutations, i.e., genetic changes, in the RB1 gene and usually occurs before the age of 5. The tumor can affect only one eye or both eyes. In the hereditary form of retinoblastoma, there is also an increased risk of malignant brain tumors occurring, in most cases this is pineoblastoma. Furthermore, secondary tumors such as malignant bone or soft tissue tumors (osteosarcoma or soft tissue sarcoma), tumors of the nasal cavity, the eye, and the eye socket, malignant skin tumors (melanomas), and brain tumors can occur during the disease.
How Is "Retinoblastoma Predisposition" Diagnosed?
Clinical Diagnostics
Retinoblastoma is suspected if one or more of the following findings are present in a person:
- Leukocoria (whitish glow of the pupil)
- Strabismus (squint)
- Changed appearance of the eye
- Reduced vision
The diagnosis of “retinoblastoma” can be clinically confirmed by an ophthalmologic examination.
Genetic Diagnostics
Hereditary retinoblastoma is suspected in the following cases:
- Any patient with a diagnosis of “retinoblastoma,” including unilateral and bilateral involvement
- Patient with retina (benign retinal tumor that is also due to a mutation in the RB1 gene; may be a precursor to retinoblastoma)
- A person in whose family a retinoblastoma has already occurred
Genetic testing is used to confirm the diagnosis of “hereditary retinoblastoma.” This involves investigating whether a mutation exists, i.e., a change in the RB1 gene. As this is a hereditary disease, blood-related family members of a person with a proven mutation should also be genetically tested.
Further Clinical Features
Clinically, a distinction is made between unilateral, bilateral, and trilateral retinoblastoma.
Unilateral Retinoblastoma:
In this form, only one eye is affected. Around 60% of all retinoblastoma patients have unilateral retinoblastoma, while only 10-15% of patients with hereditary retinoblastoma have unilateral retinoblastoma. The average age at diagnosis is 24 months.
Bilateral Retinoblastom:
In this form, both eyes are affected. Around 40% of all retinoblastoma patients have bilateral retinoblastoma, and most patients with hereditary retinoblastoma have the disease on both sides. The average age at diagnosis is 15 months. At the time of diagnosis, both eyes are usually already affected.
Trilateral Retinoblastom:
In this form, a malignant brain tumor occurs alongside the bilateral (or rarely unilateral) retinoblastoma. This is usually a pineoblastoma, but tumors located centrally in the middle cranial fossa have also been described.
Other Tumors:
Patients with retinoblastoma have an increased risk of developing other tumors outside the eye, called secondary tumors. These include
- Osteosarcomas (malignant bone tumors)
- Soft tissue sarcomas, most commonly leiomyosarcomas (malignant tumors of smooth muscle) or rhabdomyosarcomas (malignant tumors of soft tissue)
- Melanoma (malignant tumors of the skin, called “black skin cancer”)
These usually develop in adolescence or adulthood. The likelihood of secondary tumors is significantly increased in retinoblastoma patients who have previously received percutaneous radiation therapy.
What Is the Risk of Cancer?
If there is a mutation on both alleles, i.e., both copies of the RB1 gene, retinoblastoma develops in 90-95% of cases. In the hereditary form, this is usually bilateral, i.e., it affects both eyes. The probability that patients with bilateral retinoblastoma will also develop a malignant brain tumor, usually a pineoblastoma, is around 5%. The probability is <2% for patients who have not received radiotherapy. The survival rate for patients with retinoblastoma localized in the eye is >95% due to early diagnosis and adequate treatment.
The risk of developing secondary tumors depends on whether or not percutaneous irradiation was previously performed. For patients with previous radiotherapy, the probability of developing a second tumor by the age of 50 is 38%, and for patients without previous radiotherapy, it is 21%. The average age at the onset of a second tumor is between 15 and 17 years.
What Is Known About the Development of "Retinoblastoma Predisposition"?
Retinoblastoma is caused by a mutation, i.e., a change in the RB1 gene. This gene codes for the RB protein, an essential part of cell regulation. This protein prevents damaged genetic information from being replicated in our cells, which is a protective mechanism of our body. However, suppose the gene is present in a mutated form. In that case, the corresponding protein is not produced correctly and cannot fulfill its function, leading to tumor development.
The hereditary form of retinoblastoma is present in around 40% of patients. In our body, each gene is present in duplicate, so we have two alleles per gene. These patients have a mutated allele of the RB1 gene, making them heterozygous. In 80% of cases, this mutation originates from a new mutation, known as a de novo mutation, in the mother’s egg cell or the father’s sperm cell. For retinoblastoma to develop, however, both alleles of the RB1 gene must be mutated. Suppose the first mutation mentioned above is already present. In that case, a second mutation occurs in the retinal precursor cells in around 95% of cases so that the second allele of the RB1 gene is also mutated, leading to the development of retinoblastoma.
The hereditary form of retinoblastoma is an autosomal dominant inheritance, whereby the mutation of one allele is inherited from one parent, and the mutation of the other allele arises spontaneously in the retinal precursor cells.
Is There Any Form of Treatment Available?
The treatment of retinoblastoma depends on many factors and should be planned and carried out in collaboration with pediatric oncologists, ophthalmologists, pathologists, and radiotherapists. The priority is to remove the tumor to ensure survival and, if possible, to preserve vision while avoiding secondary tumors. The choice of therapy varies depending on the stage of the cancer, the location and size of the tumor, the number of tumors, the occurrence and type of tumors not located in the eye, and the available resources. Treatment options include local and systemic chemotherapy, cold therapy, laser therapy, internal radiation therapy, removal of the eyeball, and, as a last resort, percutaneous radiation therapy.
If possible, any form of ionizing radiation, including X-ray, CT, and percutaneous radiation, should be avoided to minimize the risk of secondary tumors.
Diagnosis of " Retinoblastoma Predisposition" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " Retinoblastoma Predisposition" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
Genetic Counseling
This plays a significant role for patients with hereditary retinoblastoma, particularly in screening examinations and the risk of developing secondary tumors, as well as the care of siblings. Furthermore, genetic counseling should be carried out again when retinoblastoma survivors reach childbearing age.
Examinations for Early Detection
For patients with hereditary retinoblastoma or a positive family history (i.e., at least one family member has retinoblastoma), the following examinations are suggested:
Prevention of Retinoblastoma in the Eye
< Tabelle seitlich verschiebbar >
| Age | Frequency |
|---|---|
| Birth to 8 weeks | Examinations without sedation every 2 to 4 weeks |
| 8 weeks to 12 months | Examinations under sedation monthly |
| 12 to 24 months | Examinations under sedation every 2 months |
| 24 to 36 months | Examinations under sedation every 3 months |
| 36 to 48 months | Examinations under sedation every 4 months |
| 48 to 60 months | Examinations under sedation every 6 months |
| 5 to 7 years | Examinations without sedation every 6 months |
< Tabelle seitlich verschiebbar >
Prevention of Trilateral Retinoblastoma (Retinoblastoma in the Eye & Brain Tumor)
- MRI of the head at the time of diagnosis
- Some centers recommend an MRI of the head every 6 months until the age of 5 years
Prevention of Secondary Tumors
- Patients are informed about the risk of secondary tumors, that they should be aware of any new signs or symptoms, and then consult a doctor.
- Skin examinations should be carried out as part of regular childhood check-ups, which the family doctor or a dermatologist should continue annually.
- Some centers recommend annual whole-body MRI examinations from the age of 8.
Diagnostics Before Birth
Due to a lack of data, no standardized recommendation is yet available.
According to current knowledge, a more favorable outcome in terms of therapy-related consequences is not to be expected for patients in whom the tumor disposition has already been determined prenatally. Prenatal diagnostics motivated in this regard are therefore not recommended in Germany.
When examining the eyes as part of the U1 examination, attention should be paid to signs of retinoblastoma that may already be recognizable (leukocoria, strabismus). The first ophthalmological examination for the early detection of retinoblastoma should be carried out in an ophthalmology center specializing in retinoblastoma within 14 days of birth.
Ophthalmologic examinations for early detection are not recognizably required if predictive diagnostics immediately after birth have ruled out the possibility that the child has inherited the known disease-causing change in the family (targeted examination). For this purpose, the parents’ declaration of consent should be obtained prenatally so that umbilical cord vein blood can be taken at birth for genetic diagnostics. A report of the findings is available within 1 week in the case of most pathogenic changes and thus before the date of the otherwise necessary first ophthalmological examination in a center specializing in retinoblastomas.
Retinoblastoma Predisposition – What You Can Do Yourself
You Should Pay Attention to This
To minimize the risk of secondary tumors, any form of ionizing radiation, including X-ray, CT, and percutaneous radiation, should be avoided if possible.
Patients who have survived retinoblastoma should always consult a doctor if new complaints or symptoms of any kind occur so that any secondary tumors can be detected and treated as early as possible.
Furthermore, patients who have survived retinoblastoma should undergo genetic counseling if they are of childbearing age.
Further Information
Patients can also register for the CPS registry at any time or have this done by their doctors in charge.
Any further questions?
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