Is it indicated to screen the other twin for retinoblastoma if one twin is diagnosed with the condition, especially in identical twins (monozygotic twins)?

Screening for Retinoblastoma in the Twin of an Affected Baby

Yes, the unaffected twin should be screened for retinoblastoma when one twin is diagnosed with the condition, especially in identical twins, due to the high risk of hereditary disease. 1, 2

Genetic Basis and Risk Assessment

• Retinoblastoma is caused by biallelic mutations in the RB1 gene, with one mutation that may be germline (hereditary) or somatic and a second mutation that is always somatic 3
• Approximately 40% of retinoblastoma cases are hereditary due to germline mutations in the RB1 gene 4
• In identical (monozygotic) twins, the risk of both twins developing retinoblastoma is significantly higher due to shared genetic material 2
• Even in fraternal (dizygotic) twins, screening is essential as they may still share hereditary mutations 2

Screening Recommendations

• The American College of Medical Genetics and Genomics recommends referral for genetic counseling when a single case of retinoblastoma is present in a patient or first-degree relative (including twins) 1
• Intensive ocular screening is recommended for all individuals with known germline RB1 mutations 4
• For twins where one is diagnosed with retinoblastoma:
  • Immediate ophthalmologic examination of the unaffected twin should be performed 2
  • Genetic testing should be conducted to determine if the twins are identical or fraternal 2
  • DNA profiling is mandatory for genetic screening in families with twins to guide appropriate counseling and surveillance 2

Surveillance Protocol

• Early detection is critical as it maximizes visual sparing and improves outcomes 1
• Ophthalmologic examinations under anesthesia should be performed at frequent intervals for the unaffected twin 4
• If genetic testing confirms a germline RB1 mutation in the affected twin, the unaffected twin should undergo genetic testing as well 3
• If genetic testing is not immediately available, frequent screening should be implemented while testing is pending 1

Special Considerations for Twins

• Twin pregnancies have a higher incidence of congenital anomalies, particularly in monozygotic twins 1
• Studies have demonstrated retinoblastoma discordance in twins, emphasizing the importance of genetic analysis for both twins even when only one is affected 2
• Determining zygosity (whether twins are identical or fraternal) is crucial for risk assessment and surveillance planning 2

Long-term Surveillance

• Children with hereditary retinoblastoma have approximately 20% risk of developing second primary cancers, particularly if they received radiotherapy 4
• Long-term surveillance may be necessary not only for retinoblastoma but also for other potential malignancies 4
• Neuroimaging for pineoblastoma surveillance is recommended for patients with germline RB1 mutations 4

Common Pitfalls to Avoid

• Failing to screen the unaffected twin promptly after diagnosis in the affected twin 2
• Not performing genetic testing to determine zygosity in similar-looking twins 2
• Assuming fraternal twins have no increased risk when one twin is affected 2
• Delaying screening while waiting for genetic test results 1
• Not providing appropriate genetic counseling to the family regarding inheritance risks for future offspring 3

Early detection through proper screening of the unaffected twin can significantly improve outcomes by allowing for early intervention and treatment, ultimately preserving vision and reducing mortality 5.