Our Trip to Holland

On Tuesday afternoon, we received a call from Giuliana's genetics doctor. I was quite surprised, as they said it would be at least 2-3 months before we received the results of Giuliana's methylation analysis, and it's only been 2 1/2 weeks. The test came back positive confirming Giuliana does have Beckwith Wiedemann Syndrome. She has Hypomethylation of the Long QT gene, and two of the paternal chromosome 11. Joe and I welcome any questions you may have. We don't want this to be the elephant in the room. And. . .honestly. . .for me anyway, it helps with acceptance to talk about it, and it helps me understand it better each time I explain it.

I was angry in the beginning because I felt the doctors kept saying she has Beckwith Wiedemann Syndrome because they wanted her to have it. It's so rare, what are the odds? 1/13,000 actually. Maybe we should play the lottery! Now that she's been diagnosed, I am so happy that they sugggested all of this testing and kept mentioning BWS to us so I could research it and be prepared. All of Giuliana's doctors have been supportive of the idea of BWS, and have never said no to us seeing a specialist or having a blood test. I have found some support groups online to help me handle everything. One of the moderators sent me an email with this short story that couldn't express how I'm feeling any better.

Welcome to Holland

By: Emily Perl Kingley

I am often asked to describe the experience of raising a child with a disability to try to help people who have not shared that unique experience to understand it, to imagine how it would feel. It's like this.

When you're going to have a baby it's like planning a fabulous vacation trip to Italy. You buy a bunch of guidebooks and make your wonderful plans. The Coliseum... Michaelangelo's David... the gondolas of Venice. You may learn some handy phrases in Italian. It's all very exciting.

After months of eager anticipation, the day finally arrives. You pack your bags and off you go. Several hours later, the plane lands. The stewardess comes in and says, "Welcome to Holland."

"Holland?!?" you say. "What do you mean Holland? I signed up for Italy. I'm supposed to be in Italy. All my life I've dreamed of going to Italy."

"But there's been a change of plans," says the stewardess. "They've landed in Holland and there you must stay."

The important thing is that you haven't landed in a horrible, disgusting, filthy place full of pestilence, famine and disease. It's just a different place

So you must go out and buy new guidebooks. And you must learn a whole new language. And you will meet a whole new group of people you would never have met.

It's just a different place. It's slower paced than Italy, less flashy than Italy. But after you have been there awhile and you catch your breath, you look around and you begin to notice that Holland has windmills, Holland has tulips, Holland even has Rembrandts.

But everyone you know is busy coming and going from Italy, and they're all bragging about a wonderful time they had there. And for the rest of your life you will say, "Yes, I was supposed to go. That's where I had planned."

And the pain of that will never, ever go away because the loss of that dream was a very significant loss. But if you spend your life mourning the fact that you didn't get to Italy, you may never be free to enjoy the very special and lovely things about Holland.

Dr. Rita gave me a website to visit to help me understand the genetics side of Giuliana's Beckwith Wiedemann Syndrome (BWS). It is very complicated and I still don't fully understand it, but I will do my best to explain.

Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 11, one from each parent, form one of the pairs. 10 - 20% of cases of BWS are caused by a genetic change called paternal uniparental disomy (UPD). Paternal UPD causes people to have extra copies of genes that are only active on the paternal copy of the chromosome. People with paternal UPD are also missing genes that are active only on the maternal copy of the chromosome. In BWS, paternal UPD usually occurs in early embryonic develpoment and only affects some of the body's cells. Giuliana has 2 paternal copies of chromosome 11.

She also has Hypomethylation on the Long QT gene. It is also called the KCNQ1OT1 gene. The KCNQ1OT1 gene is located within another gene called KCNQ1. Unlike the KCNQ1 gene, which provides instructions for making a protein that acts as a potassium channel, the KCNQ1OT1 gene does not contain instructions for making a protein. Instead, a molecule called a noncoding RNA, is produced from the KCNQ1OT1 gene. This RNA helps regulate genes that are essential for normal growth and development before birth.

People inherit one copy of most genes from each parent. Both copies are typically active, or "turned on" in cells. The KCNQ1OT1 gene is only active when it's inherited from a person's father. The KCNQ1OT1 gene is part of a cluster of genes that are controlled by a nearby region of DNA known as imprinting center 2 (ICR2). Several of the genes in this cluster are thought to help regulate growth.

At least half of all case of BWS result from changes called methylation that affects the ICR2 region. Methylation is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. In many people with BWS, the ICR2 region has too few methyl groups attached (Hypomethylation).

This abnormality disrupts the regulation of several genes that are normally controlled by ICR2. Specifically, hypomethylation of the ICR2 region leads to an increase of the activity of the KCNQ1OT1 gene and a reduction of activity of other nearby genes. Because some of these genes are involved in directing growth, a loss of their activity leads to overgrowth (Giuliana's tongue), an increased risk of tumors, and other characteristics of BWS.

The two types of cancer that BWS children are prone to are called Wilms Tumor (affects the kidneys) and hepatoblastoma (affects the liver). The best thing we can do for her is have her screened for these cancers. Early detection is the key. If she does develop one of these cancers, by catching it early, it reduces the amount of chemo she would need along with other drugs. As I mentioned before, we will have her blood drawn every 6 weeks until she is 4 to check her AFP levels, and an abdominal ultrasound every 3 months until she is 8 to look for tumors. Once she is 8, then we will have a more personal discussion with the doctors to see if it is necessary to continue screening. When she becomes age 10, her risk of cancer is the same as anybody else.

There is a tongue reduction (TR) surgery available. So far, ALL of Giuliana's doctors and therapists see this surgery as radical and not necessary unless her breathing and eating is affected. It is best/ more helpful for children to have this surgery between 18-24 months old. We currently have a Home Pulse Oximeter to measure Giuliana's oxygen levels at night. So far she is doing well, and her oxygen levels only drop below 89% when she wakes up and cries for her bottle in the middle of the night. Otherwise she is up at 97, 98, 99, 100%! So that's a good thing that her tongue is not blocking her airway. We have an ENT appointment next week where we will discuss this with the doctor and he will let us know where we go from here. Dr. Marshal is in St. Louis, and it seems like he speializes in BWS children and TRs. Most contact with him is via email and mail with pictures. We have not decided if we are going to contact Dr. Marshal for Giuliana.

She is also eating superbly! She is smiling, cooing, babbling, and even trying to rollover by herself! She already rolls from stomach to back, but is working on back to tummy.

Joe and I want to thank everyone for your support and words of encouragement. Stay tuned for more of Giuliana to come!