Thursday, July 12, 2018

News from July

BCH Genetics just gave us the update that Jessica’s x-inactivation in her blood is 100:0.
Duke had studied Alexis’ x-inactivation and found it to be 100:0 as well in her blood.  It’s more difficult to study in other tissues because both Alexis and Jessica need those other tissues J.  They could take samples, but I’m not sure we’re (collectively) smart enough to know what goes on with the body in the process of x-inactivation

If you have seen the kids in real life or even in photos you can perceive they are “different” from each other.  But yet, it almost looks like they have the same genetic differences.  That’s very bizarre and I’m sure we’ll eventually understand how gene deletions can manifest in physical characteristics and capabilities. 

In the meantime, we continue to raise our beautiful cheerful children.

What have we been doing over the past month?
We joined a new family.  Ok, probably a little exaggeration, we still have our own families.  Some background – when we were undiagnosed, we participated in the CHARGE Syndrome Foundation activities because a lot of Alexis’ medical needs overlapped with CHARGE Syndrome.
But we attended the biennial Cornelia de Lange Conference in Minnesota.  We met our new family – our home in the genetic landscape.  We had a difference experience than some of the other families we met:
a)   It wasn’t our first family conference (we had attended 4 CHARGE Conferences)
b)   We were recently diagnosed (like Jessica was diagnosed 2 weeks before the conference)
c)    We had a definitive genetic diagnosis – other families were diagnosed clinically (& were pursuing genetic diagnosis)

The best things about conference:
a)   Meeting our new family – connecting with the tribe (see article by the great Susannah Fox about why this is important) 
b)   Finding 2 other families with the same gene – HDAC8.  One family has a daughter who is 15, one has a daughter who is 3.  If you re-read my old blog post, you will see that I hunt because I want to find out what future Alexis(+Jessica) will be and also be able to help the path for new families.
c)    Interacting with leading Cornelia de Lange researchers and clinicians.  Wow, was that a fun ride!  One of the things that Cornelia de LangeFoundation does at their conferences – they have clinicians (=Doctors) who specialize in CdLS and you can make 30min appointments (=no cost) with them.  It was fabulous. More on this later
d)   Learning more about life and love in Cornelia de Lange.  Wow.  I was mesmerized by how quickly we were pulled into the CdLS family.  What beautiful humans.

Regarding the clinicians – because we only had Alexis’ diagnosis during conference planning time – I organized for us to visit 3 clinicians.  Here are the updates for Alexis:
a)   Orthopedics – we discussed Alexis’ tightness and looseness.  We were able to talk about her foot bracing, her overnight leg splints, her back brace, and her standing/walking/interests.  The doctor agreed with our plan
 i) continue with leg/foot bracing
ii) continue with time in the stander (she understood how Alexis really didn’t like the leg / knee immobilizers)
ii) try really hard to get Alexis comfortable with the body jacket / back brace – hopefully we will get this on Monday July 16 (we are scared it will make Alexis grumpy – especially since she has to sleep at night with her CPAP and right now we’re not sure how comfortable back brace will be in her usual sleeping position)
iv) our plan for 3 week intensive PT in August is prudent.  By having structure and repetition, Alexis could make good progress.  We are going to NAPA Center – for 3 weeks in August for 5 hours each day.  Alexis will be very grumpy with us – but hopefully they will help make it fun for her! 
v) consider doing knee casts if we want to explore non-surgical options to loosen her hamstrings
vi) consider serial foot casting if we want to explore non-surgical options to loosen her gastrocs
b)   Dentistry – we discussed Alexis’ lack of teeth (we allowed BCH to extract 8 baby teeth November 5, 2015).  We have 1 permanent tooth trying to emerge now….. Very nicely, he said it was not in Alexis’ best interest to have that many teeth extracted (we have regretted this for a long time). So we will proceed with what we have and he was impressed with her hygiene and said it would just take a while for her to get permanent teeth. 
c)    Gynecology – we discussed some aspects of precocious puberty.  Fun topics.  Matt enjoyed this consult (J not really at all)

Here are the updates for Jessica:
a)   Orthopedics – continue with foot orthotics (shoe inserts).  We don’t need to explore anything more elaborate if podiatrist prescribed orthotics are working fine.  She is tight in her gastrocs as well and needs to do daily stretching.
b)   Dentistry – we are fine proceeding ahead with local dentistry support (aka, we don’t need to take her to BCH for dentistry).  We do need to be careful with both kids on general anesthesia – as CdLS kids can have unique reactions to anesthesia.  Jessica had 1 palate expander but the dentist suggested that she could potentially benefit from using it again.  We will explore this with the orthodontist soon. 
c)    Genetics – We hadn’t originally planned to speak with Genetics since we had just spent 2 days at CHOP in April.  But alas, with Jessica’s new diagnosis – it was great to meet with Dr Kline from GBMC (She’s the director of Pediatric Genetics at the Harvey Institute of Human Genetics).  She asked a lot of the same questions that Dr Krantz (CHOP) and like us was perplexed by the different presentations of the same genetic deletion.  She asked for our kids’ genetics work-up information to be sent to her.  I suppose with geneticists from Duke, Baltimore, Philadelphia, Boston (& Alabama) we’re starting to get our genetic pose together! 

Ok, I should be quiet for a while.  It’s probably an overload of information – that ping pongs around in my head most days.  If I’m back to blogging, hopefully writing some of this down will help organize the ping-pong balls in my head!  (I can only hope…..)

Take care and Happy Summer!!!

Saturday, June 16, 2018

Tough Topics

Back in the day, I picked engineering.  I also picked math and I picked Spanish - these were my degrees in school.
When my science-loving-sister defended her PhD years later, I sat dumb-founded at how little I understood about genes, mechanisms, loci, etc.  I used some of those words in school, but usually talking about math or engineering applications - not for plants or human body, for sure!

Here is HDAC8 in all of it's glory.  This is definitely the part of genetics articles that I just look at like a pure foreign language.  

I'm getting there, I can understand differences between mutations and deletions and mosaicisms and germline mosaicisms.  I can even grasp x-inactivation which heavens knew I didn't a clue what that was until June 2017 (when Duke informed me that Alexis was 100:0 x-inactivation).

In the meantime, I called this blog post "Tough Topics."  For sure understanding the actual reason for my kids to have CdLS is tough.

But it was the conversations yesterday with Jessica.  Before school, I chatted with her about her new diagnosis.  She was at all of the appointments where I had described my logic to the doctors and obviously she was the one that gave blood for the testing.  So she should know the outcome of the testing.  I explained that she and Alexis were sisters but stronger than that - they were special sisters that shared a disorder that made some things in life challenging for them.  That Alexis' challenges were greater (feeding, walking, engaging with the world) - and that Jessica had worked very hard to overcome her challenges.

As we were lying in bed at the end of the day (usually watching silly cat or dog videos), I asked her if she wanted to read what I had written about her diagnosis and Alexis' diagnosis on our Family Blog.  She has read other things on the blog, so it's possible she would read those two posts without me around to answer the questions.  We read them. 

Then the tough conversation - in Alexis' blog post I wrote this:
We know someone very close who had a daughter with CdLS who passed away.  

Jessica didn't know the person, I knew the person from a parent leadership class I had taken when Alexis was 4 or 5.  Jessica asked how old was the daughter who passed away?  I said "I think she was older, maybe 25."  Jessica reacted saying "25 is not older.  That's young."  Mom fail.  She's known of CHARGE kids who have passed away, but clearly I have to remember that she's adjusting to a new normal. I will have to craft my conversations better.  

Then she came up with the next question somewhat out of the blue.  To understand Jessica's brain connections, you have to remember all conversations.  Earlier in the week, Jessica had said to me "Mom, I'm going to be a great mommy - I mean not now, I'm too young.  But when I'm old enough, I'm going to be a great mommy."  And I said "yes, you are going to be a great mommy.  Definitely too young now, but I'll happily be a grandma to your sweet babies."  Flash forward to last night - after the brief brush with a topic of mortality - she comes up with "Mommy, will I be able to have babies at all?"  And all I had in me was a "I don't know yet. We have to learn some more."

So, that's the tough topics.  This kid who is challenged by so much, boiled life down into the essence in two brief interactions.

So, scientists / geneticists / doctors - get on it!  When I used to comment that we wouldn't know about Alexis' diagnosis until she was 50, you proved me wrong!  But now, you and I (with what genetics / medical understanding I can muster) - we must answer Jessica's questions!

Friday, June 15, 2018

The sky is blue..... and other updates

The last time I posted on the blog was October, to let the Schnaderbeck blog world know about Alexis' new found diagnosis.

For a long time, I had told people that part of the motivation for me to find a diagnosis for Alexis was so I could learn more about Jessica.

Perhaps people thought it was a bizarre idea.  But I had been their mother, I had seen the similarities.  Ironically, I've been seeing patterns in data and observations of people since my PhD.  It's hard to be an engineer - a deep problem solver without an inquisitive personality, a resolve to get to root cause and the stamina to improve.  And I had been that kid that asked all adults every day, "Why?"  It wasn't enough for my little brain to know that the sky was blue, I needed to know why the sky was blue.  

Here's the pattern that I saw:
-Alexis and Jessica had the same heart defect, yes Atrial Septal Defect is a frequent heart defect. Indeed every child is born with one but within 4 days the body sends a signal that says "ok heart, you're out of the uterus, your lungs are breathing air, you don't need that hole anymore, close up".  Both of my kids had fenestrated (swiss cheese) ASD.  So what?  Both seasoned Cardiac surgeons at BCH commented "Wow, I've never seen that before" when they finished their surgeries of my kids. It's not really something you expect to hear from BCH (currently #2 USNews ranking).  At the time they did Jessica's open heart surgery, they were repairing 1000 ASDs per year.  They see a lot of hearts and if they both needed to comment on the wholes they saw in my kids' hearts, it was relevant.  And also it's a perplexing - like both of my kids - the body sent the signal to the heart to start the close up process but then something told it "ok, you're done enough...."
-Jessica didn't learn to talk until 3. To begin with, I thought it was because Jessica didn't have an older sibling to learn from.  Originally we were working on sign language with Alexis, so fortunately by age 3, Jessica had over 100 signs that she regularly used.  She wasn't without a mode of communication, she was just without a mode that a lot of the world understood.
-Jessica needed PT, OT, feeding therapy as a child.  She struggled a lot with eating:
  1) as an infant, she only could take milk from a certain bottle, at a certain temperature
  2) at about 9 months old, she gave up the bottle but couldn't learn a sippy cup.  We worked with pediatrician to make sure she stayed hydrated although her whole diet consisted of baby food purees.
  3) even starting kindergarten, she didn't have the jaw strength for many foods (meats, stringy vegetables). 
  4)  now, she still struggles chewing meat or drinking too fast
  For PT, she received services from Early Intervention, School and Northeast Rehab. She can walk, jump, skip and do a lot of normal things.  She struggles to ride a bike, throw, catch - anything that is a multi-step PT action.  She did intensive months of PT three times a week, called interactive metronome which seems bizarre but really helped her with cross body coordination.  
  For OT, she received help for tying shoes, regulating her body, handwriting, coordinating fine motor movements. Thankfully all of our OT, PT, feeding friends had worked with Alexis and came to know our family very well.
-Jessica always had perplexing GI issues. First sign was Greek Yogurt. All the rage when she was a toddler to get kids away from traditional yogurt, it would make Jessica barf.  Like within 15mins of eating Greek Yogurt, she would barf (thankfully not a whole lot).  If she ate ice cream or too much cake icing, she will have "GI symptoms" (interpret as you will) - but it required after every birthday party or ice cream field trip, we needed to find a restroom within 15mins of consumption.  Thankfully, we manage this now through modified diet (avoid dairy) and culturelle.
-Jessica was diagnosed with Auditory Processing Disorder.  She doesn't hear at all in loud environments (cafeteria, gym, hallway, basketball game, movies, even classroom).  If you read about kids with Auditory Processing Disorder, it's as if they are deaf in these environments.  At school, Jessica has benefited from an FM system (microphone attached to the teacher, hearing aid in Jessica's ear). When she first got it (after 2 years of kindergarten), she came home and said "I can hear my teacher."  I can't imagine how she managed to learn anything in the first 6 years of life if "she couldn't hear her teacher".  
-Jessica continues to be a sensory kid. She wants to know routines, she gets overstressed if plans change, if expectations for the day are not met. 
-Jessica is missing 3 adult teeth - both the orthodontist and dentist have now commented on how rare this is.  Jessica also has a high palate, no cleft like Alexis, but a high palate none the less.  And will require orthodontics just to get her adult teeth to fit in her mouth (yes she has some crookedness but she is more detrimentally affected by the crowding).  On the subject of teeth, her baby teeth came in late - and she still has only lost 8 teeth, and only has gotten back 5 in their place.  (She's 10).
-Jessica has shorter 5th fingers and 4th toes. She also has leg length discrepancy which caused slight scoliosis 4 years ago.  Oh and while all other families I know buy shoes each and every year, sometimes several times a year for their kids.  Jessica has been in the same shoes for 2 years and she has small feet (can't say Tiny, because Tiny goes to Alexis).
-Jessica has a small spot of vitiligo on her upper thigh and a cafe au lait mark in her arm pit. 
-Jessica has myopia, needs glasses.  Probably really in the "so what" category, but relevant.
-Jessica struggles in school.  She learns well as long as the information is presented multiple times and best in a small group setting.  

So why do I outline all of this (somethings I've probably forgotten)?  

When we did Alexis' testing, I pushed Duke Geneticists to "please test Jessica while you're testing Alexis."  Nope, they say no.

When we joined the Cornelia de Lange Facebook group last fall, I saw the wide variety of kids who have Cornelia de Lange.  

When we visited CHOP in April, I did at least get the Children's Hospital of Philadelphia to take some hand and head measurements.  They are the experts in Alexis' syndrome, Cornelia de Lange.

But thankfully BCH genetics listened.  They heard my concerns and they agreed to take blood work, get insurance to cover it, and sent Jessica's blood to be tested for Cornelia de Lange HDAC8 deletion.

Yesterday they called back.  

Jessica has Cornelia de Lange, the same rare deletion that Alexis has.  The same rare deletion that Geneticists determined was 'de novo' in Alexis.  I haven't done my full deep investigations yet, but I have talked to the experts I know well (Dr Rose - all things medical, Dr Rose - all things genetics).  BCH Genetic counselor told me yesterday that they have seen siblings with same deletions or mutations when one parent has "germline mosaicism"

I've shared this link before with readers -
Now you can go back and re-read with an eye on the list above for Jessica.  

Silver lining in the blue sky - Jessica will remain an awesome kid.  We have already been paying close attention to the recommended treatments, not because we knew of the diagnosis, but because reacted to her struggles and only knew the path that Alexis was on.  So Jessica already has cardiologist, GI, neurologist, psychologist, audiologist and PT/OT/SLP in her world.  We now need to do some more testing with them (GI / neurology), but nothing some phone calls to BCH can't resolve.  

P.S.  If you get deep into the math of this link (see paragraph on prevalence):

I will confirm this math at Cornelia de Lange conference in MN (we are all attending). 
Typical Cornelia de Lange prevalence 1:50,000 (reads as 1 in 50,000 births will have CdLS)
HDAC8 is 5% of typical Cornelia de Lange:  so HDAC8 prevalence is 
1: 5,000,000 (reads as 1 in 5,000,000 births)  
I guess my kids are rarer than 1 in 5,000,000 births - but I am ever so lucky to be their mom.

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.