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Ultima Vez Modificado: 27 de abril del 2008
Dear OncoLink "Ask The Experts,"
I have two sons. They have two uncles, both of whom had bilateral retinoblastoma as infants. The uncles’ older brother (my boys’ father) did not ever develop it. He has never been tested. The uncles were born in the late ‘50s. My boys were born in the ‘70’s and had their retinas examined under general anesthesia periodically until they were two years old. My question is: can you determine a percentage of chance that my boys could have children that would have retinoblastoma?
Eric Shinohara, MD, Resident in the Department of Radiation Oncology at The University of Pennsylvania Medical Center, responds:
Given the available information, we can hazard a guess at the risk (making certain assumptions), but we cannot provide an exact percentage chance that your grandchildren will have retinoblastoma. It appears from your information above that two of three brothers had bilateral retinoblastoma, while the oldest brother, the father of your children, did not develop retinoblastoma. This suggests that one of the brothers’ parents carried a defective retinoblastoma gene. One possibility is that two of the brothers inherited the defective gene, and then unfortunately developed a second defect in the other copy of the retinoblastoma gene, thus resulting in the disease. In this scenario, the eldest brother did not inherit a copy of the gene, just by chance. Another possibility is that all three brothers inherited one defective gene, but the father of your children simply never had a second mutation and so he never manifested the disease. Yet a third and far less likely possibility is that - by complete chance - the two brothers with retinoblastoma both developed the sporadic form of the disease resulting in retinoblastoma, while the father of your children did not.
Based on these assumptions, the father of your children could have either: 1) inherited a single copy of the defective retinoblastoma gene (without ever manifesting signs of the disease from this single defect), or 2) be completely free of the mutation. Hence, it is impossible to know for certain whether your children are carriers of the defective retinoblastoma gene or not with the information we have at present.
Unfortunately, as you can see from the above discussion, it is impossible to determine the exact percentage risk. I would encourage you to contact a genetic counselor near you to discuss genetic testing with you and your family, and to see if further testing could help to determine the risk to your sons' children. Most genetic testing does require the testing of an affected individual, in this case one of the uncles, to identify the defective gene, if one is present. In some cases, tumor specimens that are stored can be used for testing, but the time that has passed since the cases were diagnosed makes this unlikely. To find a genetic counselor near you to discuss the options, you can use the search feature at the NCI site.
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