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!

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 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014191/

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):  https://www.ncbi.nlm.nih.gov/books/NBK1104/

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.