Remember this post?? http://babyclairesblog.blogspot.com/2011/04/androgenetic-biparental-mosaicism.html You may want to read back through it first before reading this to refresh your memory. I know it's long, but it will help things make more sense instead of retyping it all again.
Ok, now that you have been refreshed from the previous posting, here we go. Dr. K basically said: "The results from our molecular studies are consistent with Androgenetic Biparental Mosaicism in Claire's liver tumor and placenta. No androgentic cells were detected in her blood, but the sensitivity of the assay is uncertain and low levels of androgenetic cells might be missed in the blood. In other published cases of ABM, blood often has no detectable androgenetic cells, possibly because they are not able to form mature blood cells or get out competed by biparental (normal) cells in the blood lineage." Since that somewhat made sense, he offered to discuss it over the phone so I called him last night to do just that.
Basically, Dr. K said the findings don't really change anything. It just means that we now understand what happened with Claire. He analyzed 5 samples - my blood, Trent's blood, Claire's blood, Claire's placenta tissue, and Claire's liver tissue. ABM basically means that there are excess paternal alleles in the cells. He tried to explain how they determine if there are excess alleles. In normal (biparental) cells, there should be a 1:1 ratio of maternal and paternal cells or really close to 1:1. The actual normal range is 0.8 to 1.8. When he tested my blood and Trent's blood, ours came back within the normal ranges between 0.9 and 1.3. When he tested Claire's liver and placental tissue, the ratios were outside of the norm. The paternal allele is overrepresented. He said this is EXACTLY what you would predict for ABM, PMD, and HMH (all of which Claire had/has).
The reason Claire's blood sample looked normal was because either it is normal and there are no ABM cells in her blood or the normal cells out compete the ABM cells. Or the testing that they use may not be sensitive enough to detect the ABM cells. It's so new they don't have a handle on how sensitive the testing needs to be to detect these cells in blood.
I asked the genetic questions. Would this reoccur in subsequent pregnancies of ours? Is this a genetic thing that either Trent and/or I passed on? Is this something Claire can pass on to her children? What they THINK they KNOW (this is doctor talk for "we are pretty sure we know, but can't make promises because you might sue us) to date is that they are unaware of any reported recurrences in subsequent pregnancies. So that's good news. And it's not something we passed on to Claire. I will explain that in a moment. They only have about 6 years worth of research on this so they can't say what it can or can't do in 30 years. And they can't say if it will or will not affect Claire's children. They just haven't tracked it that long. From what I understood, there have been only 3 cases EVER so far that have been clinically tested (not research tested) and Claire is 2 of those 3 tests. So yeah........
So to somewhat try to describe what actually happens to cause ABM which causes PMD and HMH (and could have possibly caused the Tetralogy of Fallot but they won't know that since they didn't get heart tissue to test) is this:
During the EARLIEST stage of fertilization of the egg, the cell is comprised of 1/2 a chromosome set from the dad and 1/2 a chromosome set from the mom. The "mysterious part" that they know happens but don't know why it happens, is next. Something happens and the pronucleus from the dad divides. So instead of 50% mom and 50% dad, you now have 75% dad and 25% mom. In the very next stage (the very first few cell divisions after fertilization) there is a "corrective phenomenon" where the cells divide again and then there are 3 paternal cells to 1 maternal cell. So if I understand it looks like this:
1 mom and 1 dad = normal biparental daughter cell
1 dad and 1 dad = androgenetic biparental daughter cell
So Dr. K said that one cell is "normal" (having 23 chromosomes from mom and 23 chromosomes from dad) and the second cell is not normal (having 46 chromosomes like a normal cell, but all 46 are from the dad). Both sets of cells continue to divide to create the fetus and it looks like the ABM cells (all paternal cells) present themselves in the placenta and fetus (and liver in Claire and possibly other organs/places we don't know about). The doctors think that androgenetic cells (ABM) are not capable of doing what biparental (normal) cells can do. But they do know that ABM cells can make a bad placenta like mine with PMD, they can confirm that it puts the liver at risk for HMH that Claire had/has, and they think that ABM does not produce mature blood cells (since they can't detect them in the blood samples).
What they DON'T know is where all the androngenetic cells are in Claire's body and what that means for her.
They DO know that PMD (Placental Mesenchymal Dysplasia - the issues I had with Claire's placenta) is associated pretty much 100% of the time with ABM. They DO know that patients with PMD are at risk for HMH (Hepatic Mesenchymal Hamartomas - the liver cysts Claire had/has). They DO know that there is an increased likelihood to see hemangiomas with ABM (Claire does not have any that we know of). And they DO know that there is an increase chance of having Beckwith Wiedemann Syndrome with ABM (that we do not think Claire has). He said that we would be able to tell if Claire had full-blown BWS just by looking at her. They DO know that PMD is most frequently reported with ABM.
In terms of Claire - no one knows what it means for her now or in the future. That is somewhat reassuring but really somewhat daunting. I mean, they haven't found out anything that would show that we would need to be worried about anything. But at the same time, there has been less than 10 years worth of research (doctors didn't know about ABM until 6 years ago) on this, so they just don't have any data.
Dr. K said the good news was that if having ABM dramatically increased the risk for something else, you would have seen hints of it in by now in literature and it's just not there. So he said that was "reassuring."
On the flip side, Dr. K said that we know that Claire has ABM cells in her liver tumor so they are probably in her liver. And it's possible the ABM cells are in other parts of her body. The heart defect she has could be unrelated, but he suspects that this anomaly is from ABM. The cells could be really anywhere in her body and that runs the risk of them behaving abnormally at some point. But if she is at risk for that, there is not a huge increase in risk and there have been no reports of hints of anything like that happening in the literature.
Dr. K said that ABM has probably been around since the beginning of time. It's just that people never knew what it was or just didn't report it. People have PMD all the time but just don't know it or it doesn't get diagnosed and reported. With my original diagnosis, it wasn't PMD but severe placental hydrops. Until I pressed for more testing and research, that's what it would have been. Now we know that it really was PMD. He also said that ABM was recognized with PMD but is SO RARE along with HMH. HMH is a very rare tumor.
He did say we should be encouraged rather than discouraged. So that's good. I asked if he thought there was something that caused this weird error to happen right after fertilization. His hypothesis is that could us or Claire have possibly been predisposed to something to cause the error in cell division? He can't prove that anything like that happened. But he said it has been proven so far that there have been no reported recurrences in families. So that's reassuring. He mentioned again that most of the cases of ABM that they see have occurred in in-vitro fertilization probably due to the manipulation of the cells outside of the body promoting abnormal division. But in our case of natural conception, they have no idea.
So from Claire's standpoint, he said it was good to just know about the ABM, PMD, HMH connection. And to know that she has ABM cells present in parts of her body although we don't know every location. He said it was also good to know about the association with BWS in case something ever comes up that might be a place to start looking. He said it was good to have Claire's doctors aware since all of these things are just so completely rare.
So I guess my intuitions were right once again that I knew these things had to be related and that they weren't just coincidence. Was I hoping that ABM wasn't the cause and that they were just some fluke things? Of course. But does ABM change things? Not at all. It does give us some answers and that is a good thing.
Since you have endured this long, acronym-filled, medical jargon post, I will leave you with a cute picture of Claire in her jeggings yesterday! ;)
Love,
The Scott Family
What they DON'T know is where all the androngenetic cells are in Claire's body and what that means for her.
They DO know that PMD (Placental Mesenchymal Dysplasia - the issues I had with Claire's placenta) is associated pretty much 100% of the time with ABM. They DO know that patients with PMD are at risk for HMH (Hepatic Mesenchymal Hamartomas - the liver cysts Claire had/has). They DO know that there is an increased likelihood to see hemangiomas with ABM (Claire does not have any that we know of). And they DO know that there is an increase chance of having Beckwith Wiedemann Syndrome with ABM (that we do not think Claire has). He said that we would be able to tell if Claire had full-blown BWS just by looking at her. They DO know that PMD is most frequently reported with ABM.
In terms of Claire - no one knows what it means for her now or in the future. That is somewhat reassuring but really somewhat daunting. I mean, they haven't found out anything that would show that we would need to be worried about anything. But at the same time, there has been less than 10 years worth of research (doctors didn't know about ABM until 6 years ago) on this, so they just don't have any data.
Dr. K said the good news was that if having ABM dramatically increased the risk for something else, you would have seen hints of it in by now in literature and it's just not there. So he said that was "reassuring."
On the flip side, Dr. K said that we know that Claire has ABM cells in her liver tumor so they are probably in her liver. And it's possible the ABM cells are in other parts of her body. The heart defect she has could be unrelated, but he suspects that this anomaly is from ABM. The cells could be really anywhere in her body and that runs the risk of them behaving abnormally at some point. But if she is at risk for that, there is not a huge increase in risk and there have been no reports of hints of anything like that happening in the literature.
Dr. K said that ABM has probably been around since the beginning of time. It's just that people never knew what it was or just didn't report it. People have PMD all the time but just don't know it or it doesn't get diagnosed and reported. With my original diagnosis, it wasn't PMD but severe placental hydrops. Until I pressed for more testing and research, that's what it would have been. Now we know that it really was PMD. He also said that ABM was recognized with PMD but is SO RARE along with HMH. HMH is a very rare tumor.
He did say we should be encouraged rather than discouraged. So that's good. I asked if he thought there was something that caused this weird error to happen right after fertilization. His hypothesis is that could us or Claire have possibly been predisposed to something to cause the error in cell division? He can't prove that anything like that happened. But he said it has been proven so far that there have been no reported recurrences in families. So that's reassuring. He mentioned again that most of the cases of ABM that they see have occurred in in-vitro fertilization probably due to the manipulation of the cells outside of the body promoting abnormal division. But in our case of natural conception, they have no idea.
So from Claire's standpoint, he said it was good to just know about the ABM, PMD, HMH connection. And to know that she has ABM cells present in parts of her body although we don't know every location. He said it was also good to know about the association with BWS in case something ever comes up that might be a place to start looking. He said it was good to have Claire's doctors aware since all of these things are just so completely rare.
So I guess my intuitions were right once again that I knew these things had to be related and that they weren't just coincidence. Was I hoping that ABM wasn't the cause and that they were just some fluke things? Of course. But does ABM change things? Not at all. It does give us some answers and that is a good thing.
Since you have endured this long, acronym-filled, medical jargon post, I will leave you with a cute picture of Claire in her jeggings yesterday! ;)
Love,
The Scott Family
Okay, those leggings are the cutest thing, ever!
ReplyDeleteMommy-gut is rarely wrong. <3