Sunday, October 1, 2017

Finding a home in the genetic landscape

We've been a medical mystery to geneticist for a long time.  Better said, we've been a medical mystery to many specialties of doctors for a long time.  As a longtime fan of Car Talk, I like to say that Alexis has "stumped the chumps" (no disrespect to doctors).  Literally, every time we're seen by a new doctor (and even some of our existing doctors), they ask "what is her diagnosis?" We've been a person without a home.  We've looked at many options in 11 years.  

A brief reminder of her journey:
-2006:  Karyotype testing, Signature Chip (including 22q deletion and CHARGE/CHD7 deletion), Smitih-Lemli-Opitz (all testing normal) (done through Tufts/NEMC and BCH)
-2008:  Cornelia de Lange (screened for NIPBL and SMC1A deletions) - testing normal (done through Children's Hospital Philadelphia)
-2009:  Duane Radial Ray Syndrome (DRRS) / Okihiro Syndrome - testing normal (done through BCH)
-2010:  Signature Chip showed Xq13.1 deletion, which includes a gene that is associated with Glycogen Storage Disease type IXd (testing done through BCH)
-2012:  Alexis participated in Whole Genome Sequencing testing at Duke - nothing identified
-2015:  Alexis enrolled in new Undiagnosed Diseases Network program at Duke to perform additional testing.
-2017:  Alexis determined to have skewed X-inactivation in her blood (in a normal cell in girls, the cell must inactivate one of the X - since they have 2).  Alexis is found to inactivate mom's X 100%, which means it's skewed from the normal 50%-50%.

What we learned on Friday - our definitive diagnosis.  As with the typical "genetics odyssey" - it's the collection of data and information along the trip that is useful.  The true beauty is we are uncovering new understandings and the speed of sharing is saving lives.

In investigating Alexis' Whole Genome, Duke found that Alexis has a 43kb deletion on her X (at 13.1) that includes the Glycogen Storage Disease type IXd (confirmation of the 2010 testing) AND HDAC8. 

And researchers at Children's Hospital of Philadelphia have identified other gene deletions that cause Cornelia de Lange - including HDAC8. 

So, Alexis' diagnosis is Cornelia de Lange.  
      You can read more about Cornelia de Lange at 

Finding a home in the genetic landscape is nice:
-we have a network of families we can learn from
-they already have deep history and research efforts under way to help identify new treatments
-it gives an idea of life expectancy (no limits other than the underlying medical conditions)
-they have a national conference every 2 years (MN in June 2018, here we come!)
-they have centers of excellence through US and world (CHOP!)
-we have a name we can tell doctors, they will recognize it and be able to refer to published literature
-we get to build on what we already know and what we've learned from our providers (doctors/nurses/therapists) and networks (CHARGE Syndrome families, MA medically complex families, etc)
-read and learn a ton more!!!

In the past 48 hours, I've been reading a lot on the website.  I encourage the curious of you to look at that as well.

I will throw in a caveat, as with most everything Alexis is very unique.  Of the kids that present with Cornelia de Lange, only 5% of the HDAC8 deletion.  So, if you read something on the CdLS website that doesn't jive with your impression or interaction with Alexis - it may mean what is presented reflects the larger population.  It doesn't change our diagnosis, but this PDF article explains some of the biggest differences between the smaller HDAC8 deletion and the 'usual' Cornelia de Lange population.  One of the biggest differences is that they describe these kids with a happy disposition.

And lastly, Alexis still continues to challenge geneticists.  She has two X chromosomes.  If she is truly 100% X-inactivation through all cells in her body, it doesn't make sense as to why the deletion on the inactivated X is affecting her.  Skewed X-inactivation is relatively new area of research - so while we have a diagnosis that makes sense for Alexis, the science hasn't fully caught up.  They do see this X-inactivation more commonly with kids missing HDAC8, but they are still seeking to fully understand this.

Some people have asked me how I feel about the diagnosis?
-We have a home. I've read some of the articles here They describe very accurately interacting with Alexis.
-We have been doing all of the right things (see publications above about therapies and benefits).  We have the right doctors, we have the right specialties, we have the right concerns.  Imaging you've been on a highway "thinking you're headed the right direction" and after 11 years of driving, you have confirmation that you're on the right highway.  Relief.
-We have encountered a CdLS family at a Perkins Conference before and it was always a curiosity that Alexis didn't have the genetics for CdLS
-As we felt with some of the CHARGE families at our first conferences, I will wait with anticipation to 2018 in MN to join our physical home.  In the meantime, I've joined the CdLS Facebook group and I'm sure I have a lot to learn.  I especially can't wait to connect with other families.
-Alexis' path has never been easy. We have always known that she had differences.  We know someone very close who had a daughter with CdLS who passed away.  We know that with or without a diagnosis, our vigilance and care for Alexis is our top priority.
Reserved Happiness or Peace
-It's hard to say you can be happy if you read all of the list of things that are going to challenge a kid with CdLS.  But there is great peace knowing that we've been doing the right things, connecting the right dots and pushing for a diagnosis.
-I am happy that even though Cornelia de Lange is a rare disease, it's not uber rare.  It's not that we will be hunting for families across the Internet - Cornelia de Lange already has a rich and deep network. 

And most of all, I am thrilled because no matter what Alexis' genetic material has said or kept secret for all of these years, she is still fighting to live a beautiful and rich life.  She is providing joy and happiness to all.  She is still inspiring us to make the world a better place.

Friday, December 23, 2016

Merry Christmas and Happy New Year!

Hello everyone! 
We were very late (or not at all) on our Christmas cards this year!

Hopefully a virtual one with make folks happy!

Wednesday, October 19, 2016

Way Back Thursday

Someone asked for some of our family photos, so I dug these up from my archive.  Enjoy!

Thursday, August 18, 2016

First Communion Photos

We did the kids first communion in April, but I'm just getting around to posting the photos.  I hope you enjoy.

Monday, June 6, 2016

Hole in the Wall Gang Camp Photos and Videos!

Over the weekend, we went to the Hole in the Wall Gang Camp in Ashford, CT.  It is truly a special place on earth for special families.  We were lucky enough to participate in the first Rare Disease Family weekend.  It was tremendous fun for the whole family.  I think the photos will show!
Jessica never passes up an opportunity to be a cat!

Alexis relaxing after lunch on Friday.

Dad and Jessica fishing.  I had hoped to get a natural photo, but instead Dad told Jessica to smile - so I got the corny silly faces from Jessica and Dad.

Alexis and Dad makes silly faces at the folks dancing in the circle!

Last day - Jessica sad about having to leave the baby dolls at camp. (She had adopted them for the weekend)

Our 'fake Chowdah' - tribute that I painted while we were at camp.

Alexis was not interested in the fish that Dad caught. At All.

And it wouldn't be all done without some videos!  Sorry for the shaky / unfocused  -- I have other talents. :-)
Alexis performs with Julian, the Music Director at Camp.
Jessica reads a story to the baby dolls on stage.
Kids & Matt & Julian in Jam Session in the Sound Studio before the Stage Night.

We made kites!  Proof that they actually fly!!

Matt has the videos of the zip line on his phone.  Jessica, Matt and I participated - but I swear Jessica made the climbing wall look a lot easier than it was!

Friday, February 12, 2016

Someone(s) Special Dance

Tonight, Jessica invited me to her Someone Special Dance at school.  It is meant for the kids to invite a grandparent or parent or family friend or someone in their life who is special.  Well, I got to see first hand who is the really special one.

Most folks know how special we consider Alexis, our miracle girl (who just turned 10 - a topic for a different post).  But most don't know much about Jessica - other than her open heart surgery - now 4 years in the past.

But you haven't heard much of her learning struggles or her struggles at school. But let's just say between repeating kindergarten and being diagnosed with an auditory processing disorder, she's been working tremendously hard to make up for the fact that her first words weren't until age 3. Her IEP is nearly as long as Alexis' and both are making tremendous progress this year.

Let's set the stage for the night - Jessica in her fanciest dress (from Christmas party times).  Me having come literally from the construction work-site, changed into a dress - as Jessica requested.  We left for the dance, as we're going in - Jessica skipping and giddy.  Then does some self talk (out loud) "Jessica, Calm down, don't hurt your friends when you get inside!"  I echoed that's a great idea - I'm very proud of you for remembering to prepare yourself.  

We danced for a little while, took a cookie and water break to regroup.  Then we went back in, Jessica noticed a little boy and mom.  The mom was holding the little boy because clearly he was overwhelmed.  We danced some more.  Probably an hour went by.  We noticed the little boy crying - shoulders shaking and all.  I thought - Jessica has an incredible visual memory.  I remembered seeing the little boy with his mom, but I didn't remember anything about the mom.  I asked Jessica if she could tell me what the mom looked like - she did say "she's wearing a gray sweater."  To get us closer to finding his mom to help the boy, I said "Jessica, can you walk around with me to find his mom."  I knew she would be able to figure this out quickly.  2 seconds later, we're taking the mom to her son.  He was so relieved.  
Jessica is my someone special.  She noticed him originally with his mom.  She noticed him crying uncontrollably.  She used her spectacular visual memory to help us find the mom and rescue a very anxious and concerned kid.  Jessica struggles with so much that others take for granted, but she has empathy beyond her years and awesome skills to be extremely helpful. I was so proud.

We returned to dancing but Jessica really didn't want to leave my side (which also meant that I had to continue dancing-no skills at that). During the last 15 minutes, Jessica's friends ran up to her and asked if she would like to dance with them.  She wanted to but was extremely concerned about leaving my side.  But when she finally ran off with them, she was smiling and happy. Those little girls were truly the "someones special" to my dear Jessica.  Jessica was over the moon that one of the last songs was the song she had requested earlier from the DJ -- Taylor Swift "Bad Blood".  I couldn't have been happier and proud that my someone special was seen as someone special by her classmates.  

Jessica is fast asleep and I'm ready to decompress from a full day at work and then 2hrs of K-5 dancing!  

Monday, December 14, 2015

Loving the girls!

Our girls are the sweetest on the planet.

Tonight, I put Jessica to bed - she was beside me whimpering. I asked 'what's wrong bug?'  She said, "I want a baby sister".  I explained that we have Alexis and Jessica and they were awesome.  Then she says, "What if me and Alexis were twins!"  I said "oh that'd just be silly! You are almost twins, practically!"  Then we got distracted by talking about how Alexis would always be just 1 year older than Jessica.

On any other day and time, this conversation would leave my mind quickly. But it didn't tonight because tomorrow is the 10 year anniversary that we found out that Alexis' twin, Kaitlyn, had died.  Probably similar weather 10 years ago - I don't remember it being snowy - just cold and wet.  I remember because from the back of the ambulance, you only get to see the traffic behind you and the distortion of their headlights as go down the road.  

We have the sweetest girls because no matter what scars Mom and Dad carry around, they are always happy and content with everything.  We aren't without struggles, but in the "for real" - we have it good.  The struggles we have might bring us down, might trip us up, and may cause us to dream up new plans.  But from it all, I am grateful. Sweet kids, happy house, busy life and new chapters.  Alexis is amazes us everyday - she is getting so strong and doing so well. Here's a basketball video from last week: 

Evidently she did like 15 in a row until the camera came out.  Silly goose!  Matt filmed another one of her tonight - I'll try to get that one posted soon.

And then Jessica's sweet piano concert.  You might be able to tell when she had to look back at her music to find the next note (she had it memorized until that point).  Love her.  She is so proud of herself.  Yes, we can work on the performance - but we won't change the performance (if you know what I mean).  

Happy Holidays to you all!  Give your families and friends extra hugs this week - we all need them!