Androgenetic Biparental Mosaicism, Placental Mesenchymal Dysplasia, Hepatic Mesenchymal Hamartomas, and Beckwith-Wiedemann Syndrome

I literally just spent the last 2 hours writing this post and then it got deleted.  I cannot believe it.  I am going to try to retype it again.  I know it will not be as good as the last one.  

Those 4 things in the title of the blog are a mouth full, but mean a lot to us.  This is going to be an extremely long post, so if you don’t have time, come back! 

I will start from the beginning since that is the best way I know how to explain everything in the subject of the blog.  I was obviously pregnant with Claire when we went to find out the sex of the baby.  At the ultrasound, we immediately saw she was a girl!  But then the US technician spent a lot of time scanning the placenta, I was wondering what was wrong.  We saw the ob/gyn after the US and he confirmed we were having a girl.  But then he said the US tech noticed that my placenta didn’t look normal, so they wanted to send me to ECU to get a level 2 ultrasound.  I had already been told that I may have a small bleed behind my placenta and I had been having regular spotting.  So this scared me to death!

This is the ultrsound on July 23rd where the placental cysts were first seen.  On the far left of the picture, you can see the black circles.  Those are the cysts.



Of course we found this out at 5 pm on a Friday.  So I spent all weekend trying to Google what could be wrong with the placenta.  I knew the doctor had said something about possible cysts or aneurysms.  But I couldn’t really find anything online.  And by now you know that when I hear something bad, I tune out everything else after that.  So Monday morning I called the doctor back to see if he would mind going over it again with me.  He wasn’t sure why I was so “concerned.”  His exact words to me were:  “Frankly, I am not worried about it.  It’s not a big deal!”  Little did he know…..

To try to make a really, really long story short – we went to ECU, the doctor saw the “placental mass” and said it was probably a cluster of cysts or aneurysms.  We would just watch it and make sure it didn’t take over the placenta.  At this same appointment is where she noticed something not quite right with Claire’s heart.  We came back for the fetal echo where they diagnosed Claire with tetralogy, and at this appointment they noticed a small spot on Claire’s liver.  So thank God for the US tech that noticed something not right with the placenta that allowed us to find the tetralogy and liver cyst early enough.  (This version is WAY shorter than the one I had already typed!!!!!!)

We went to Duke on September 3^rd to get a second opinion.  The ob/gyn there confirmed the tetralogy and also noted the liver cyst.  At this appointment, the cyst was bigger than Claire’s heart and stomach – it had grown a lot since they first saw it about a week before.  The ob/gyn said that day that the cyst may become the priority for Claire over her heart.  I did not believe him.  What could be more important than her heart issue??  But he ended up being right. 

This is Claire's face on the right with her head pointing towards the right.  You can see her nose bone well.  The big black circle on the left is the liver cyst on September 3rd at Duke. 

A profile picture of Claire's face and body.  You can still see the large black circle which is the liver cyst on September 3rd at Duke. 

So a few weeks later, I became really swollen and looked 9 months pregnant instead of 6 months pregnant.  We all just thought it was the fluid catching up with me.  Little did I know that a few days later I would be in pre-term labor at Duke at 28 weeks.  The Wednesday and Thursday that I was first at Duke are a blur.  I was on so much magnesium sulfate it’s not funny.   I couldn’t see straight, had no reflexes, and felt like I was on fire all in an effort to stop the contractions. 

Luckily, that Thursday, the ob/gyn working that day was the one who saw us on September 3^rd so he was familiar with our situation.  I don’t remember much that day, but I do remember that he said that Claire’s liver cyst had taken over her body.  It was not allowing her to swallow the amniotic fluid therefore the fluid had backed up inside my belly and put me in labor.  It was a do or die situation literally.  They were going to have to drain the cyst in-utero and also drain amniotic fluid right then or both Claire and my life were in danger.  These doctors, nor any other Duke doctors, had done this procedure before according to him.  But we trusted them and they drained both.  The contractions immediately stopped. 

You have probably read “the rest of the story” about Claire’s liver cysts and the repetitive draining and the fenestration surgery she had.  After the fenestration surgery, they determined for sure that the cysts were Hepatic Mesenchymal Hamartomas (HMH).  Here is a medical definition/description of HMH:

Hepatic mesenchymal hamartoma is a hamartomatous growth of mesenchymal tissue in the liver of uncertain etiology.  It is a space-occupying lesion that can potentially compress adjacent organs resulting in various complications including death.  Hepatic mesenchymal hamartoma is characterized by proliferation of variably myxomatous mesenchyme and malformed bile ducts.  The differential diagnosis includes other pediatric hepatic masses.  The diagnosis is typically made during infancy, and complete resection is invariably curative.  (Arch Pathol Lab Med. 2006; 130:1567-1569)

In the research that I have done, I have found that the HMHs are very rare and very fatal to the baby.   A lot of them are undetected in-utero and therefore they crush the fetus’ heart or other organs and the baby dies.  Thank God again for that US tech that sent us for the level 2 US.  If she had not recommended that, then we probably wouldn’t have had another “routine” ultrasound the outcome could have been a lot worse. 

This is the MRI of Claire's abdomen before the fenestration sugery.  The big white circle is the large/original cyst.  As you can see, it took over her whole abdomen. 

In the meantime, the placenta was being analyzed in the lab at Duke.  They came back with a diagnosis of “severe placental hyrops” which means severe placental cysts.  The doctor said there was not just one mass of cysts, but rather the whole placenta was now cystic.  It was very big and was the consistency of a 40 week old placenta and was out of steam.  By then my mind was turning.   Didn’t it make sense to anyone but me that the placental cysts probably had something to do with the liver cysts???  It was just coincidental.  But none of the doctors could tell me yes or no.  Everything is just so rare, there is just not a lot of data on it. 

So my mind got to thinking….and I started doing my own research online.  The more I read about HMH, the more I became thankful that Claire is still alive.  I also started trying to make the connection between the placenta and the liver cysts.  I found several medical journals making the connection between something called Placental Mesenchymal Dysplasia (PMD) and HMH.  Once I read what PMD consisted of, I knew right then and there that Claire’s placenta had PMD!  And the ultrasound pictures online of PMD matched my ultrasound images.  And there is a link between the PMD an HMH! 

Here is a description of PMD that I found online:

placental mesenchymal dysplasia

HP:10377

Placental mesenchymal dysplasia is a rare human placental disorder in which the placenta is enlarged and contains cystic villi and dilated vasculature. In contrast to a partial mole, mesenchymal dysplasia may coexist with a normal fetus.
Synopsis
 placenta enlarged with abnormal, large, and often cystic villi
 placental dilated and/or thick-walled vessels
 large, hydropic stem villi
 myxomatous stroma
 cistern formation
 ’chorangiomatoid’ changes
Etiology
 normal karyotype (89%) (15791673)
 abnormal karyotype (11%) (15791673)

• trisomy 13
• Klinefelter syndrome (47,XXY)
• 69,XXX triploidy

 Beckwith-Wiedemann syndrome (23%) (15791673)
Differential diagnosis
 partial hydatidiform mole

• In contrast to a partial mole, it can coexist with a fully viable fetus.

Associations
 Fetal anatomical and vascular anomalies

• hepatic mesenchymal hamartoma (mesenchymal hamartoma of the liver) (17378624)

References
 Francis B, Hallam L, Kecskes Z, Ellwood D, Croaker D, Kent A. Placental mesenchymal dysplasia associated with hepatic mesenchymal hamartoma in the newborn. Pediatr Dev Pathol. 2007 Jan-Feb;10(1):50-4. PMID: 17378624
 Cohen MC, Roper EC, Sebire NJ, Stanek J, Anumba DO. Placental mesenchymal dysplasia associated with fetal aneuploidy. Prenat Diagn. 2005 Mar;25(3):187-92. PMID: 15791673

So now how to prove that Claire’s placenta had PMD and not just severe placental hydrops.  I searched and found a name of one of the research pathologists who worked at Seattle Children’s Hospital.  I emailed him thinking if he emailed me back, that would be great.  And if he didn’t, it wasn’t anything lost but time.  That night he emailed me back and pretty much said without looking at the pathology slides and tissues, that he was sure the placenta had PMD. 

We talked on the phone and he suggested Duke send him the pathology information so he could take a look at it.  Fortunately, I was able to contact one of the best ob/gyns at Duke and she helped me out.  She forwarded my request to the Duke pathologist and he sent the information to the Seattle pathologist.  A few days later, the Seattle doctor emailed me his clinical findings with the diagnosis of PMD and confirming the HMH.  Great!  We are getting somewhere!!!

He had also mentioned Androgenetic Biparental Mosaicism and Beckwith-Wiedemann Syndrome, but I will get more to that later.  For now, we know that PMD can cause HMH.  So the connection has been made.  Sometimes I wondered if the doctors didn’t push the issue because they didn’t want me to feel like it was something I did to create Claire’s liver issues.  But deep down, I have known the whole time the two were connected.  We had even discussed “mirroring syndrome” at one point where her body was mirroring mine with the cysts.  But now we have a medical diagnosis and a medical reason for the HMH.  

So now that I had the connection made between me and Claire I felt better just knowing.  But remember the Seattle doctor mentioned ABM and BWS.  So what is ABM?  Well, I am not completely sure.  I have done some reading on it and he explained it to me the best he could over the phone.  For someone who has not been to medical school, I somewhat understood the basics of ABM.  I know that it is a fairly new thing that they are researching.  And he believes that ABM is the cause of most PMD. 

From what I understood, ABM is a “random error” that occurs in the DNA of the fetus right after fertilization.  The fetus still has the normal 46 chromosomes, but in some of the chromosomes, the fetus can have more of one parental allele than the other.  Basically you are supposed to have an even number of maternal and paternal alleles.  But ABM is where some of the chromosomes are uneven.  This error can cause the PMD and HMH or other defects.  But more commonly PMD and HMH. 

I don’t know a whole lot about the ABM yet.  I am still learning.  The Seattle doctor suggested we see a geneticist so she could do some testing and better explain things.  Not all PMD and HMH are caused by ABM.  But as they research it, they are seeing it more and more.  To test for ABM, I, Trent, and Claire would have to get blood drawn.  I think that’s it.  As far as do they think it could happen again???  They don’t think so since it’s a “random error.”  What does it mean for Claire if her liver has ABM cells in it?  I don’t know.  Could other organs in her body have ABM?  Possibly. 

So we have made an appointment with a geneticist at Duke.  Fortunately, this geneticist is also a cardiologist and has seen Claire on occasion while she was at Duke.  So she’s somewhat familiar with Claire.  And we like her! 

Then onto the Beckwith-Wiedemann Syndrome (BWS).  Of course when he said this I blurted out that Claire had been tested for chromosomal disorders through my amniotic fluid and her blood, and they both came back as normal.  But as with the Di George Syndrome, they have to send of special test for BWS.  Basically with Di George or BWS, the baby still has the normal number of chromosomes.  So it wouldn’t show up on the tests that she had.  They would have to specifically test for BWS since it is just a deformity of one of the 46 chromosomes. 

I immediately looked up BWS online to see if Claire had any of the symptoms or signs of it.  Here is what I found about BWS:

What is Beckwith-Wiedemann syndrome?

Beckwith-Wiedemann syndrome is a condition that affects many parts of the body. It is classified as an overgrowth syndrome, which means that affected infants are considerably larger than normal (macrosomia) and continue to grow and gain weight at an unusual rate during childhood. Growth begins to slow by about age 8, and adults with this condition are not unusually tall. In some children with Beckwith-Wiedemann syndrome, specific parts of the body may grow abnormally large, leading to an asymmetric or uneven appearance. This unusual growth pattern is known as hemihyperplasia.

The signs and symptoms of Beckwith-Wiedemann syndrome vary among affected individuals. Many people with this condition are born with an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. Other abdominal wall defects, such as a soft out-pouching around the belly-button (an umbilical hernia), are also common. Most infants with Beckwith-Wiedemann syndrome have an abnormally large tongue (macroglossia), which may interfere with breathing, swallowing, and speaking. Other major features of this condition include abnormally large abdominal organs (visceromegaly), creases or pits in the skin near the ears, low blood sugar (hypoglycemia) in infancy, and kidney abnormalities.

Children with Beckwith-Wiedemann syndrome are at an increased risk of developing several types of cancerous and noncancerous tumors, particularly a rare form of kidney cancer called Wilms tumor, a cancer of muscle tissue called rhabdomyosarcoma, and a form of liver cancer called hepatoblastoma. Tumors develop in about 10 percent of people with this condition and almost always appear in childhood.

About one in five infants with Beckwith-Wiedemann syndrome dies early in life from complications related to the disorder. Older children and adults are much less likely to have serious medical problems associated with the condition.

To my untrained eye, she does not have any of the signs and symptoms of BWS.  And also according to Dr. Rachel’s expert opinion of knowing and looking at Claire.  J  So I am hoping we don’t have to worry about the BWS stuff.  But the Seattle doctors said it’s sometimes associated with the ABM, PMD, and HMH, so we may investigate just to be 100% sure. 

So FRANKLY, all of this WAS a big deal.  I have yet to write a thank you note to the US technician, but I plan to do that soon.  Without her expertise, this story could have turned out way differently.  And I hope that this information can be helpful to others in the future.  I have searched for other mothers who have dealt with all of these things with no luck.  It’s just such a rarity that I guess the only things I can find are medical journals and research about it. 

We will continue to get to the bottom of everything.  I like answers.  Yes, I know that only God knows all of the answers and there is not always an answer to everything.  But when there is an answer out there, I just have to find it.  And when it comes to Claire and her health, I will search tirelessly.  Do I blame myself now for her liver cysts?  No, I don’t.  Do I want to know if this would happen again if we decided to have more children?  Yes, but I doubt I will find out that answer until it happens. 

I will continue to update the blog as we find more answers.  I hope this helps other women to know when to look deeper into their gut feelings (no pun intended). 

So congratulations on your very first class in medical school by me!  :)

Love,

The Scott Family