We're still planning on putting up more pictures from Gracie's Wish Trip, but right now I just need to update you on the less fun side of this blog. Yesterday our whole family drove to Houston to get genetic testing done so we can determine if we are at risk for developing retinoblastoma (the kids) or possibly having more children with the mutation (James and I). Now that we know where Gracie's mutation is it makes it much easier to test the rest of us because they know exactly where to look. I'll write exactly what the lab report says about Gracie's mutation, which actually is a small deletion. This way if you have a really good knowledge of genetics you'll know what I'm really talking about. Otherwise it's just blah, blah, blah.
"Quantitative multiplex-PCR, long range-PCR, and sequence analysis identified a deletion mutation called g.50965_59649del8685 in DNA from Grace's blood sample. This mutation is a deletion of 8.5kb of DNA on one allele of the RB1 gene. The deletion starts in intron 6, deletes exon 7 and extends to the beginning of exon 8 of the RB1 gene, destroying the exon 8 splice acceptor site. The deletion is expected to cause out of frame skipping of exons 7 and 8 in the mRNA transcript. This mutation is highly likely to lead to retinoblastoma."
So James and I were tested to determine if we carry this mutation and passed it on to Gracie. This is unlikely. All of our kids need to be tested because even if James and I are negative it is possible that we have a germline mosaicism. This means that we don't carry the mutation in all of our cells but we could produce multiple eggs or sperm that carry this mutation. Our other 3 kids who needed to be tested were somewhat terrified at the prospect of getting their blood drawn for the test, but in the end I think they did pretty well. Our oldest daughter who is 7 didn't really fight but because she was the last kid to get her blood drawn she was pretty nervous by the time she got in there. In fact she looked quite green. It wasn't until this morning that we decided that she was fully recovered and able to go to school.
While we were talking to the geneticist I had a couple of questions that we got really good answers to. My first question was why when Gracie has already developed 7 tumors in her eyes are her odds of developing other cancers only 51%. Not that I think that's a low percentage it's ridiculously high but she's already developed 7 separate tumors, it's not like they've spread and started to grow again. If this is the case why doesn't she get tumors all over her body all the time (at least in the cells related to the RB1 mutation). The answer is this. Your bones, and lungs, and most other areas of your body have several genes that are required to mutate before cancer starts to grow. So most organs, tissues etc. have several genes (5 or 6) there as a defense mechanism. The retina on the other hand only requires one gene to mutate in order to have a tumor start. And because one of those alleles already as a mutation in it in Gracie's case the odds are very likely. So that's why she's developed seven tumors in just 3 and a half years of life.
It's nice to know that the body has so many defense mechanisms in it. DNA is mutating all the time. Some mutations are genetic like Gracie's, but others are brought on by environmental factors. We can't do anything about the genetic mutations. But knowing they're there is a really powerful tool. We do however take as much control of the environmental factors as possible. This is why we've got Gracie a swimsuit that covers so much skin (shorts and long sleeved shirt). This is why she wears sunscreen with SPF 85 and a hat. This is why it's important that she eats a really good diet full of lots of fruits and vegetables and only limited meat. This is why she can never ever smoke, or even be around people who smoke (besides the fact that it's stinky and darn right nasty). We want to stomp out every possible environmental factor that we can. We love our little girl, and all of our other kids as well and want to take as good of care of them as we possibly can.
Stephanie
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2 comments:
Hey guys - right after we found out about Gracie's diagnosis, I took our kids to the optometrist to have them checked out as well, and I was told that children shouldn't develop the disease beyond the age of 2 or 3. Does Gracie run higher chances of developing further cancers b/c of this mutation. Can a child develop retinoblastoma without a genetic mutation? Just wondering, b/c my optometrist thought she was on the older end of being diagnosed. I just always worry b/c there is that genetic factor linking our family with yours, and wondered how closely related family members could possibly be affected. Anyway, glad that you guys are getting some answers. We hope that the results to the rest of the family turn out for the good. Thinking of you always.
Lins
Lindsay,
About 60% of retinoblastoma cases have NO genetic mutation. It just requires that both alleles of the RB1 gene mutate on their own. In this case there is only ever 1 tumor in 1 eye. If there is ever more than one tumor it is always genetic because the odds of that mutation happening spontaneously in two alleles in the exact same location in more than one retina cell is virtually impossible. On the other hand the retina isn't fully mature until a kid is 5 or 6, so they can still develop it until this time. Almost all cases of rb happen before this age while the retinoblasts are still maturing into rods and cones. Non genetic rb is usually diagnosed later than genetic rb because that one tumor really has to grow really large before it gets noticed. Genetic rb is usually diagnosed earlier because there can be so many tumors growing that they can quickly fill up the orbit. The average age for diagnosing genetic rb is 11 months (I think).
Don't worry about your kids having a genetic predisposition. Their risk is virtually non existant. Gracie is most likely the point mutation, if not her than it has to be James or I because if it went further than that we'd know we had a family history. In fact for James or I to contain the mutation and not know about it would be a miracle. But all kids should get their eyes dilated for an exam to determine that they don't have unilateral retinoblastoma. It's pain free and can be done in a doctors office and besides retinoblastoma it can diagnose a whole lot of other vision problems where early diagnosis is beneficial. Exams under anesthesia aren't required unless you actually think they might have something. Gracie's first exam was in Dr. Leishman's office in Lethbridge, with just a dilation (they put drops in to dilate the pupil) he could tell something was seriously wrong and that's when this all started. They could just as easily give everyone an all clear.
Yes, this mutation does increase Gracie's chance of other cancers. She has a 51% chance of developing other cancers. Particularly osteosarcoma (bone cancer), lung cancer, bladder cancer, skin cancer, sinus cancer, brain cancer. Well the list could go on and on, really it's any of the sarcoma's or melanomas, although the ones mentioned are even more specific. The chemotherapy we gave her increases her chances of leukemia and lymphoma as well. That's why we'd rather not do radiation and increase those risks even further. It's also why we're trying so hard to control all the environmental factors that we can. We also want to stay living near (or with easy access to) a retinoblastoma center so the doctors who work with her will understand the risks she has and treat them seriously. If she complains of pain in a joint or limb I want to know she's got a doctor who'll know how serious that can potentially be and not just shrug me off as a paranoid mom. Very few doctors know retinoblastoma well enough to understand this.
Hope this answers you questions,
Stephanie
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