We Won the Lottery!!!!! The Genetic Results are In

We did it!!  
We got some answers.  Kind of.  Maybe.
And they came in such a way that let us know once again how mindful God is of our family.  We had the privilege to attend a national genetic conference put on by Global Genes called the Patient Advocacy Summit.  I could go on forever about the incredible experiences and things I learned at this conference, but I will have to write another post for that.  Their focus was about what to do once you get a diagnosis.  We were particularly interested in this because I was hopeful we would get a diagnosis sometime soon!!  They taught us about networking and finding other diagnosed families, creating foundations, finding and funding research teams, advocating for medicine trials with the FDA, and discovering treatments and cures for these terrible rare diseases.  It was incredible!!  And I just soaked it all in hoping I could some day put this information to good use.  Little did I know what was in store...

{Keep an eye on this link.  I think at some point they will be posting the amazing presentations.}

We were on our way home from California when I decided to call GeneDx.  I was told at the conference what an amazing company they are to work with (I already knew that!!) and that they will give you an update if you call about your Whole Exome Sequencing.  So I called, and I never in a million years expected to hear this, "Your timing is impeccable.  The test is done, the results are in and a report was just faxed to your doctor."  These were our faces in response:

We were ecstatic and nervous, but we focused on the excitement!  Results were in, and we didn't know what they would be or how our world could change.  At that moment, we could just be excited.

I left a message with our pediatrician's office and got a call back.  Our doc did not understand the results at all. He said we had to contact our geneticist.  Oh boy.  Any time I call the ridiculous phone tree I'm forced to leave several messages and get a call back weeks to months later or not at all.  Not this time!!!  They called me back hours later.  They told me the results were negative for mitochondrial disease YAY!!!!!!  and that we found a couple of mutations.  That's where Part 2 of our Journey for a Diagnosis begins!!!

To sum up our results, we basically hit the genetic jackpot.  And I've decided the whole process for searching for and receiving a diagnosis is fairly similar to attempting to win the lottery:

• Winning the lottery and getting genetic answers are extremely rare.  In fact, it's so rare most people don't think it is worth the time, effort or money to try.
• Gambling is a bad habit.  So is obsessing with research and finding answers.  This habit has consumed me for three years, and I don't see it ending any time soon.
• You think winning the lottery will take away your problems, make life easier, and make you happy, but often times it doesn't.  They often find out that even money can't buy their happiness.   I already can tell that answers through genetic testing just open new doors full of frustration, questions, confusion, heartache, and at times devastation.  Certain things got easier with some answers, but many things got a lot harder.  Money cannot buy happiness, and neither can genetic results.
• Even though the odds are against you, you can't help visualize yourself winning the lottery.  You see it, hope for it, visualize what car you'd buy, where you'd live.  You convince yourself you have a chance, that you could be that rare individual to hit the jackpot.  But you find yourself left in a world of disappointment and feel as if those dreams died with the losing lottery ticket.  The same goes for genetics.  You know the odds are against you, but you hope and pray you are the exception.  You visualize what it would be like to have answers, to be one of the ones who get a name to the disease attacking your child.  You stay positive and wonder where you might go for treatment, what medicines might be out there to save your child and preserve his life.  You know that is all coming your way with genetic results.  Yet time and time again, you are left with an empty lab sheet and more questions than answers.
• Winning the lottery changes everything; it changes you.  If you are fortunate enough to win, you are caught up in this whirlwind of change.  You see the world differently.  And although you wouldn't necessarily want to go back, there are times you wish you never would have purchased that lottery ticket and things could go back to the simple times they were.  This is also true for answers.  Having answers changes everything.  It changes you as a person.  There is a whirlwind of emotions and next steps and you remind yourself this is what you wanted, but there are times you wish you could go back to life before diagnosis day.

I guess you could say we won the genetic lottery.  But not necessarily in the way we had hoped.  We got results, and results may lead to answers, but at this point nothing is conclusive.  We still have quite the journey, it's just a new journey and we have an area of focus.  But these areas of focus are rare... uber rare...super duper unbelievably rare.  So rare, we won the genetic lottery!  We were blessed with an amazing warrior boy who is the very first human to have a genetic mutation on the MN1 gene.  Because he's the first, we know next to nothing about this gene or how a mutation on it might present.  The geneticists and scientists have their work cut out for them, but I imagine at the same time they are excited.  Jayson has one more mutation. It is on the LAS1L gene (that is the number 1 before L).  There are very very few people in the history of the world with this mutation.  According to our genetic report, 5 to be exact-- two pairs of brothers who were diagnosed with Wilson-Turner Syndrome because of their symptoms (phenyotype) AND an infant boy likely from Utah who only lived to be 3 months.  I will explain more about him later.  So, in summary, we have TWO mutations.  One never seen before in the history of mankind, and the other one seen FIVE times with two completely different diseases.  Before we got these results, I assumed J would be rare, and I even processed the idea that he might be 1 case out of 100 in the history of the world kind of rare.  But I never ever entertained the idea that he would be the first, or the sixth of anything.  See, we won the lottery!!!!!  Jay is like 1 in 108 billion!!!!  Those are some incredible odds :)

Let me tell you what these results mean.  I'm not going to talk much about MN1, because J is the first and we know nothing about it.  Let's talk about LAS1L.  For the smarty-pants scientists reading this (and other special needs mommies) here are the details: 

LAS1L

X-Linked disease with intellectual disability

Varient: p.C186R

cDNA: c.556 T>C

Hemizygous

Inherited from Mother

Classification: Variant of Unknown Significance

Interpretation:
The LAS1L gene encodes a protein that is part of a novel ribosome biogenesis complex which localizes to the nucleolus.  A de novo missense pathogenic variant was identifed in an infant with spinal muscular atrophy with respiratory distress (SMARD).  In addition,, a missense pathogenic variant was identified in two unrelated families with X-linked intellectual disability.  The affects males in both families had similar clinical features including mild to moderate intellectual disability, obesity, facial features, speech impairment, variable behavioral problems, gynecomastia, small undescended testes, hypogonadism, and tapering fingers.

If you actually made it through the report with all of the medical jargon, you're either really smart or a good friend. :)  Let's talk about this, starting with the two families with the X-linked intellectual disability.  It's referring to Wilson-Turner Syndrome.  J doesn't fit there really.  He doesn't have their facial features, no real behavioral problems, no enlarged male breasts, no obesity, no tapered fingers, no short stature, and his genetalia is normal.  He does have small feet, speech impairment and an intellectual disability which fits with this diagnosis, but that is it.  I'm fairly certain he doesn't have this condition.  But now let's look at the baby infant with SMARD.  Did you catch what SMARD stands for??  Spinal Muscular Atrophy with Respiratory Distress.  SMA.  We are talking about SMA.  If you don't know about SMA, google it now.  You will find it is the number one killer for babies and children.  You will find it is a nasty neuromuscular degenerative disease.  You will find it is every parent's worst nightmare.  Well, there is a type of SMA associated with Respiratory Distress and they have named it SMARD, Spinal Muscular Atrophy with Respiratory Distress.  There is a specific gene tied to its diagnosis.  However, this baby boy with a mutation on LAS1L, the same gene that J has a mutation on, was ALSO found to have SMARD, and he didn't carry the other gene associated with SMARD.  After lots of work, effort and research, it was determined that there is a SMARD 2 that is associated with the LAS1L gene.  The research was done here in Utah by a team of doctors I know.  Crazy, right?  Well this boy did not make it.  He passed away at just three months.  He is all the research they really have right now.  But it was enough research to make a significant finding in science.  There research article is referenced a lot in genetics.  Their one study was enough to establish SMARD 2, at least at this time.

Now many of you are probably thinking at this point, "Well good, Jayson doesn't have a severe respiratory condition or a trach so there is no way he has SMARD.  LAS1L can't possibly mean a SMARD diagnosis for Jayson."  But let me walk you through my thinking process as I recalled information from Jayson's medical record filed so carefully in my head.  Maybe you remember our Sleep Study from a previous blog post,  Too Hard, but Jayson was having troubles breathing during the sleep study.  The respiratory therapist told me that the only time they had seen those breathing issues were with kids with Spinal Muscular Atrophy.

"Something about your son's lungs or brain is not triggering the back up rate.  It's like his respirations are too shallow to trigger the machine.  Our machines and very good and very sensitive.  They can pick up newborn preemies respirations, but not your son's when he's in level 3 or 4 REM sleep.  We could pick them up when he is awake or in a light sleep, but in the deep sleep the machine doesn't recognized he is attempting to breathe."  I asked her if that meant that the Bipap isn't working and she confirmed the backup rate is not kicking in so the machine is not breathing for him when he needs it.  I asked her what the next level of support is?  She was quiet.  I asked, "Trach and vent?" and she said yes, our doctor will likely talk to us about it.  She sat me down and reviewed the lines on the screen with me, how they disappear when he is in Level 3 REM sleep, and then he starts to fight for air and that's when I show up in the video trying to help him, then he breathes again and all is well again.  Once he settles in deep sleep again, the cycle continues.  She turned to me and said something that struck me, "The thing is, we only have seen this happen with Spinal Muscular Atrophy kids."  I didn't know what to think or how to respond.  She said that it would be easy for someone reading the recording from the night to assume Jayson was disconnected or there was a technical error, so they were talking directly with the reader that morning, having him talk to me about what I'm seeing at home, write a special note on the study report and ensure he calls our pulmonologist directly to let her know it is not a machine error.  It is Jayson.

So, you can imagine how it took my breath away to read the gene Jayson has a genetic mutation on has a research based connection to SMARD.  I also started to reflect on J's respiratory history...  Chronic respiratory distress as an infant, needing high flow O2 at home 24/7 then nasal cannula O2 until about 2 years of age.  Desats all night long every night even on O2 and support.  Every night numerous times he had apnea events long enough we had to stimulate him to breathe.  Then he started CPAP with O2 during sleep right before he turned 2 (I think), and now he is needing Bipap with a higher flow of O2 because his respiratory problems are progressing.  He had 4 ALTE's as a baby (Apparent Life Threatening Events) and needed us to begin the steps to CPR on three occasions.  Currently, his respiratory rate is frequently dropping below 5 and going as low as 0 on a typical night.  He doesn't recover from respiratory illness in the typical fashion and requires more support.  He does not have a trach, thank goodness, but it's been talked about numerous times.  No, I have never thought my child could fit under the SMA or SMARD diagnosis, but I'm starting to wonder given this summary of respiratory concerns.  And what stands out most about it is nobody knows why!!!!  The neurosurgeon says it's not brain.  The neurologist says it's not seizures during the night.  The ENT says it's not his airway.  The pulmonologist says it's not his lungs.  We have NO explanation.  His sleep study results are awful every time, and we have no clue why.  This would explain why.

SMARD kids often struggle to breathe due to diaphragmatic paralysis.  They like to sleep upright or folded over to remedy the diaphragm issue.  They struggle breathing at night during deep sleep laying down in the supine position.  That's when Jayson' struggles. Therefore, many of these kids choose to sleep upright in a sitting position to help their diaphragm.   If any of you have followed me on Facebook, you've probably seen dozens upon dozens of these types of photos:

Jayson prefers to sleep upright or folded over.  He gets himself in this position every single night.  I've often wondered if that is what makes it easier for him to breathe.  Maybe it's related to his diaphragm??  Lastly, I remembered that in his last chest x-ray in January there was a concern brought up about his diaphragm.  We asked our doctors about it at the time, and they didn't think it was an issue but more like a mistake in the x-ray.  Of course, I am now worried about it.  I went and looked at the x-ray report and it stated his diaphragm was elevated suggesting eventration.  When I look up eventration it tells me it is often confused with diaphragmatic paralysis on an x-ray and more testing is needed to see the difference.  In summary, the x-ray is stating the image of J's diaphragm could suggest diaphragmatic paralysis, which is the condition kids with SMARD have.

It's not looking good, my friends.  A genetic condition, breathing issues similar to that of SMARD kids found during his sleep study, and an x-ray suggesting the diaphragm condition kids with SMARD have.  I hope this explains to you all why I'm freaking out.  Maybe it doesn't. No?  Okay.   Let me explain this a little more bluntly.

SMARD is terminal.

There is no cure.

All kids end up trached.

Then they die from respiratory distress.

They don't get better.

They die.

And there are three pieces of medical evidence right now suggesting this might be my son's diagnosis, the most significant of these being the genetic findings.

So yes, I'm a mess.  But let me tell you what's keeping me going.

The other kid with the LAS1L mutation and SMARD didn't have any craniofacial abnormalities.  SMARD could explain J's respiratory issues, but what about his craniofacial features, his chiari, his craniosynostosis, his C1 hypoplasia???  Maybe LAS1L can, but right now we do not have any evidence linking LAS1L with these things.  This gene mutation may not be the one causing his issues.  We may need to look into Whole Genome Sequencing to see if there is another gene that can explain everything going on with Jayson (which I learned at the conference that Genome Sequencing is happening in particular states!!!).  Right now, nothing exactly fits.  But at the same time, that much in common with SMARD scares the daylights out of me.  Furthermore, this mutation is legit.  Legit is not scientist talk.  It's Tristin talk.  Legit meaning it is X-Linked and found in my DNA as a carrier, and in J's DNA.  That likely means something.  It's not random.  And that scares me.  And makes me very upset.  My baby could be dying, and my DNA would be to blame.  Swish that around in your mouth a bit.  It doesn't taste good, does it? :(

So what do we do now?

I read the three research papers written on LAS1L and the one linking LAS1L and SMARD was written by a team of doctors here.  I wrote the neurologist an email who was one of the main authors, letting her know another child with this mutation has been discovered, and asking for her help.  She informed me she had moved from SLC to Boston and is working with Harvard and Boston Children's now.  However, she still wants to help us!!!  And maybe she can help even more now because the technology and experience of doctors in Boston is so much better!  She plans to reanalyze Jayson's DNA samples from GeneDx and dive into Jayson's medical history and go from there.  Our current geneticist at Primary's is seeming like he may be proactive as well.  They are doing a lot of research right now and preparing for our appointment we will have on November 3.  Hopefully by then we can come up with a good plan.  He mentioned the need to insert these genetic mutation into animals and study what happens.  This has been done with the LAS1L in zebrafish, but not with the new gene mutation MN1.  I am excited when I think about all of this.  We are progressing science.  By fighting for answers for Jayson, we are contributing to the scientific world and helping other future kids who may be diagnosed.  We are a part of something important, and these amazing doctors and scientists are going to be working hard trying to find answers for my boy!  

This week has been emotional and draining.  Excitement, fear, sadness, devastation, confusion, regret, guilt, hope, anticipation.... so many emotions, and they change quickly.  I can be talking with excitement in my voice about what is happening one moment, and be crying the ugly cry the next.  I don't think I like this stage, but I tell myself at least we're moving.  We've been so stagnant for 3 years, not moving to find more answers due to our inability to have access to the Whole Exome Sequencing test.  But now we are moving in some type of direction.  GeneDx made this possible.  They restored hope in this journey and got us to this point.  They have been the key player at this point in getting answers for my son and I am eternally grateful!

They have been so easy to work with and helpful alllll along with way.  Good communication.  No surprises.  No drama.  No hidden costs.  No private agenda.  No problems.  And the report with results was so user friendly and informative.  I do not have a single critique.  If you are reading this and have been wondering if you should do Whole Exome Sequencing----------> STOP---------------->  Stop wondering, and do it.  A phone call is all it takes.  And the rest is history.  We were lucky and we were prioritized, but we went from hopelessness to potential answers in 16 weeks.  Do it.  You won't regret it!

So that's where we are at.  Our geneticist said this process will take time.  It is so hard having patience when we could be on the brink of a diagnosis, but hey, I've waited this long.  My personal focus right now is to soak up every little minute with my little man.  There has always been the possibility that his life would be short here on earth, but this new news makes this possibility seem a little more real.  I also plan to bother  work with the geneticist here and the neurologist in Boston to keep them working on finding answers.  I also plan to start building my new relationships I made at the conference with some of the most inspirational people I have ever met.  I know they will play an integral part in this journey.  And I plan to strengthen my spirituality.  This journey is hard, and quite honestly, it just keeps getting harder.  I can't do this alone.  I need all of you, and I need my Heavenly Father.  If I strengthen my relationship with Him, I know it will strengthen me.  And Jayson needs a strong mom.  He needs me at my best, and that's exactly what I intend to be.

Thank you for your prayers and support.  Our prayer for a diagnosis is in process of being answered... in God's time.