A DIAGNOSIS

After 5 years of
wondering
questioning
tests
research
tears
and prayers

Jayson finally has a....

I am still in shock.  I don't think it's completely sunk in.  I still worry someone is going to come back and say, "Never mind.  It's not what we thought."  But a big part of me wants to soak this moment in-- a moment where we have some sort of an answer.  I've dreamed of this moment for FIVE YEARS.  It doesn't seem real.

My baby is no longer UNDIAGNOSED.

We got a call in November from our geneticist's office ASKING US to come in.  I was surprised!  Last time we saw our geneticist he told us he'd follow up with us in 3-5 years.  The last thing I expected was a phone call from his office requesting an appointment.  We set it for December 20th, and I began counting down the days.  I was nervous to hope for anything to come out of it, though.  I had been disappointed by our genetics appointments so many times before, but I really wondered if we might get an update on the research being done on Jayson's MN1 mutation that began last spring.  At a recent pediatrician appointment, our doc told us that there was some progress on the research study, but he wasn't sure how much he could share with us.  Recently I had found more research posted online about deletions on MN1 (Jayson's is a mutation, not a deletion) that definitely stated that MN1 was a craniofacial gene.  When I talked with a genetic counselor about it at a Utah Rare event, she stated it may or may not mean something since the research was based on kids with a deletion not a mutation.  In my gut, I KNEW this was it.  I knew this all meant something.  I just had to wait for our research to be done and shared, and I also knew that took a lot of time.

Finally the day arrived.  I literally had to tell myself that nothing good was going to happen in the appointment to prepare myself for disappointment, but deep inside I couldn't deny my excitement.  Our geneticist Dr. V walked in with a resident and his genetic counselor and he sat on the stool, looked at me and said, "Well, where is it?  Where are your beautifully prepared notes and questions?"  I chuckled and opened my notebook to reveal the page of notes.  "Oh, hand written this time?  Where's my printed copy with pictures?"  he asked with a smile.  Truth be told, no I wasn't very prepared for this appointment like I have been in appointments past.  But I didn't request this appointment, he did.  And I've spent the past 5 years bringing pages of syndromes that could "fit" with pictures of kids with those syndromes compared to Jayson.  I learned through Whole Exome Sequencing just how rare Jayson is.  I learned that he likely had something so rare it didn't have a name or wasn't discovered yet.  There was no need for the pages of printed notes and pictures this time.

I expected him to begin the conversation since he requested the appointment, but it was silent and all eyes were on me.  So I asked the big question, "Where are we with the research being done on MN1?"  He responded, "Let's dive into it, shall we."

His next words will be ones that I will remember forever for several reasons.

He flipped through some notes in the chart and didn't make eye contact as he said, "I am not quite sure how or why I missed the research on MN1 and the mouse model last year.  I am not sure why I was so certain that MN1 was a gene of unknown significance.  It is not.  We know that now and I should have known that then."

Wait, what?!?!  I figured he was making reference to the research studies I recently found online about the deletions on MN1 and how those deletions were inserted into mice and they developed craniofacial abnormalities, just like the kids who had the deletions.  And he admitted to making a mistake last year and not taking the time to truly look into this mutation.  I respected that.  I respected that so very much.

I was completely fixated on him and frustrated I forgot to free up space on my phone so I could record every detail of our conversation.  I wanted to remember it all.

I began to ask specific questions about the study as he pulled out the spreadsheet that was a draft of the data collection in progress.

How many kids have been found and where do they live?

6 kids total.
Soak that in for a minute.
Six kids in the entire world with Jayson's genetic mutation.  That's it.
Wow.
One in Hong Kong, one in France, one in the Netherlands, one in Boston, one in California and Jayson in Utah.
Although Jayson's Whole Exome Sequencing report said he was the first to be found with his mutation, that was not correct.  He was actually the 5th out of the 6.  I'm assuming they were all discovered about the same time and weren't yet recorded in the system.

He said a geneticist in Boston was wanting our permission to discuss and share data on Jayson through an online database, and of course I gave that permission.  He said she was kind of lighting a fire under all of those involved trying to get this research all collected so it can be published. He said he had a couple of sheets for us to sign so that Jayson's medical information and pictures could be published, and that he's aware we've already signed some in the past.  I said, "Oh, I think the ones we signed were to give approval to have all of our whole exomes studied."  I didn't expect his response.

"Well, there's no need to do that now. We have a diagnosis.  We know that MN1 is responsible for Jayson's craniofacial syndrome.  Any other data from Whole Genome Sequencing would probably just confuse us, so we don't need to pursue that."

That's when it hit me.  This was it.  Not a suspicion, a thought or a hunch.  Not a possibility that we were studying.  This was it.  Jayson's diagnosis.

I asked, "I know research can take a while.  Do we know when they hope to complete it?"

"They plan to publish it this next spring."

Seriously???????  I had prepared myself for YEARS of waiting, like is often required.  I prepared myself for many more research studies and questions.  Never in my wildest dreams did I think that we would have a definitive answer that would be proven and published in spring of 2017.  Wow.  I was speechless, nearly in tears.

I asked if it was significant that all of the other children in the study had a de novo mutation as well, like Jayson (meaning it was not passed from either parent, but was a new mutation).  At first he disagreed and said he thought it was X-linked.  I insisted that it was de novo, and he proceeded to look through his paperwork and get on his computer to confirm.  He said, "I don't even know if it's been stated which chromosome this is located on.  I just don't have all of the research."  That's when I responded, "It's on the 22nd chromosome."  He stopped his search on the computer, looked at me and smiled.  "Of course you would know.  I bet you know what part."  I responded, "I used to, I think it's 22q.12.1 but I'm not sure."  He laughed out loud and shook his head.  "Then it must be de novo, you as the mother would know.  So yes, all of the children had de novo mutations.  And you want to know why that is?"  His answer took my breath away, but I understood it immediately.  "That's what we often see in lethal syndromes.  They die with the child so they don't pass on.  Either that or the child has such significant cognitive disabilities that it is never passed on."  Those are words that a mother never wants to hear, ever.  Never ever.  But I refused to dwell on that today.

I asked if that definitely means that this de novo mutation would not be passed on to other children.  He responded, "Because you guys are waiting to grow your family based on this information, aren't you?"  He hadn't heard.  It was my immense pleasure to inform him that we were pregnant, expecting a baby in June thanks to embryo adoption.  He was so very excited for us.  "But you may want more children?"  I explained, "No, I don't think so.  But can other members of our family have children with this syndrome?"  He said yes, it was possible.  He explained that genetic mutations can be passed through the gonads and not the DNA, which was something that I didn't completely understand.  So a de novo mutation can still be found passed through a family, which is unfortunate.  But it confirmed our decision to grow our family in such a unique way through embryo adoption.

I really wanted to know if the other children had medical conditions similar to Jayson's.  On the spreadsheet the doctors shared craniofacial details like small head size, space between the eyes, palate issues, skeletal abnormalitites, etc.  I wanted to know if they had all of the severe health conditions Jayson has experienced.  There wasn't much of that information complete in the chart just yet, but he said it looked like Jayson was the only child to have seizures which struck his interest.  He said, "It makes me wonder if we have a modifier effect going on where Jayson has a secondary gene mutation causing some issues.  I bet a lot of these kids do.  I bet they are all a little bit different but share this craniofacial gene."  That really struck a chord with me and I couldn't wait to share my most recent research and likely discovery.

***BIG NEWS***
I've been wanting to share this information on my blog for a while, but due to the pregnancy and my battle with illness/hyperemesis I just haven't made it happen.  During our neurology appointment last July, we once again discussed the possibility that Jayson's episodes that are plaguing him may not be seizures.  Our neurologist brought up dyskinesia and told me to look into it.  That week I did some research and watched some youtube videos to observe the movements.  It's a movement disorder and the descriptions and videos just didn't match up to what I was seeing at home.  But through my research, I was brought to a page I think I had seen before.  It was a list of epilepsy imitator conditions, including dyskinesia.  I read through the long list and put a mental check next to all of those I had researched.  Every one of them... but one.  I had never heard of Benign Paroxysmal Tonic Upgaze of Childhood before.  Not only did it catch my interest because I hadn't read about it yet, but it had the word "upgaze" in it, and Jayson's episodes include an upgaze.  I immediately saw there wasn't much research about it.  But as I read through the descriptions of the events and accompanying symptoms I got THAT feeling.  The one that told me this meant something.  I searched the condition in youtube hoping to find some videos.  Tears streamed down my face as I watched videos of episodes identical to my son's.  Sobs burst out as I watched video after video of several children who acted just like my child before, during and after episodes that even our most experienced and gifted doctors couldn't understand.  This was it.  This perfectly described Jayson's neurological condition, episodes and events.  Why hadn't our experienced doctors found this before???  Because according to the research there had only be 49 diagnosed cases in the history of the world.  That's why.  Another ridiculously rare condition.  It looks and acts just like epilepsy.  In fact, many of the kids have epilepsy and seizures in addition to these episodes.  But these episodes are unique in that they never register on an EEG nor do they cause any regression or damage found on an MRI.  They are harmless, but incredibly life impacting.  In fact the literature calls them "extremely debilitating" and they cluster up to hundreds at a time, which is what we have seen with J's episodes.
Here are a few details about PTU:

• neuro-opthalmalogical disorder
• upward deviation of eyes in episode cluters with eyes rolled back, chin held low
• begin in infancy
• jerky side to side eye movements- nystagmus
• sleep issues
• developmental & language delays, non-verbal
• vertigo
• hypotonia (low muscle tone)
• episodes typically improve over time
• can coexist with epilepsy
• episode triggers include illness, tiredness, tactile stimulations, eating, loud noises, flashing lights)
• normal EEG's, MRI's, metabolic assessments
• intermittent/persistent ataxia, unsteady gait, frequent falls 
• migraines
• body temperature issues 
• sensory issues, kids like spinning

Those of you who know Jayson or follow us regularly on Facebook would get shivers reading this.  It all fits.  Every little bit.  This explains Jayson's neurological issues to a T.  Ready for the amazing part???  There's a treatment.  Several really, but one that is consistently reported in the literature.  It's a medicine used for parkinson's disease- levodopa.  

I was really nervous to bring this to anyone's attention.  I've recently been accused of doing too much medical research as a parent by a medical professional and it sort of caused some problems.  I talked to our nurse care coordinator about it with our pediatrician's office and she was not so supportive or enthusiastic.  She said, "With all of Jayson's doctors and their experience, do you really think this is something they haven't thought of?"  I told her about how rare it was and she said she still believed it would have been considered.  I felt discouraged and afraid to mention it again.  But weeks later I ended up on the phone with a neurology nurse to set up an appointment.  She told us our neuro was booked months out and even though our visit notes said to follow up in a month, she wondered if we could wait longer.  I told her Jayson had been doing really well, but there was a neuro condition I wanted to talk to our doctor about.  She said for her own curiosity she wanted to know what it was.  I mentioned it and we had a dialogue about it.  She was intrigued herself.  I didn't expect that she would relay it to our neurologist.  But a week later, I got a phone call from our neurologist to discuss PTU.  He said he agreed that it was a real possibility for Jayson.  I brought up levodopa and he said that was exactly why he called.  He was certain enough about it, he wanted to call in levodopa/carbidopa to our pharmacy right away to try.  I was ecstatic and so hopeful!!  A couple of days after starting Sinemet (levodopa and carbidopa) we watched the miracles trickle in.  (I'm crying typing this!!)  Jayson started producing crazy amounts of sounds like we've never heard before.  He started making more eye contact, following some simple directions, responding to his name, craving more interaction, and his mood and energy greatly improved!  His dysautonomia flares calmed nearly completely and his low heart rate elevated.  After about 2 weeks, his upgaze episodes DISAPPEARED.  It was our miracle drug we had always prayed for.  Jayson's school noticed a difference and suddenly his notes home were showing he was 90% on task instead of 50-75%.  They noticed he was happy, hyper and had much more energy.  His stamina improved.  Everyone around us noticed a difference and we suddenly were living this wonderful life we had dreamed of.  Our child's neuro issues that plagued him all but disappeared and he has been his best self we had ever seen!

 

 

So how does this tie in with our genetic visit?  Well, let me tell you :)  Some/many of the kids with this diagnosis are being found to have a particular gene mutation called CACNA1A.  It affects calcium channels in the body.  Want to hear the crazy part?  When I researched the mutation CACNA1A something unexpected popped up.  This is the gene responsible for a condition called Familial Hemiplegic Migraines.  Want to know who has hemiplegic migraines that run in her family?  ME!  They are rare, and either you develop them idiopathically or they run in your family.  I haven family members who suffer from them, so that makes them genetic.  Therefore, it can be assumed, I have this gene mutation.  It can be passed on... to Jayson, perhaps.  When I told my geneticist all of this information, it was incredible to watch him light up!  He questioned Mike about my migraines and how scary they must be.  He had so many questions for me and was so amazed to meet someone with this condition.  He said this HAS to mean something.  This HAS to make sense.  He said this mutation combined with Jayson's MN1 mutation would explain Jayson and his complex conditions!  He was also very interested in confirming I have this mutation.  Our geneticist quizzed me and asked, "Why wouldn't this have shown up in Jayson's Whole Exome Sequencing, especially since we sequenced you as well?"  I responded, "Well, we were looking for a craniofacial syndrome, the main syndrome causing Jayson's problems.  We listed all conditions and at that point we just said he had epilepsy.  We didn't know he had PTU.  And since my migraines didn't relate to anything craniofacial, I don't even know that I listed that as a condition for me.  Every parent and child share many mutations.  The sequencing would only look for, identify and list the ones that seemed significant.  CACNA1A didn't seem significant at the time."  He said, "You're right," and smiled.  Instead of requesting our insurance pay for more testing, we are asking GeneDx to reanalyze our data.  We are so hopeful that they will discover this as a shared mutation between me and Jayson.  It would explain so much and then our search for answers really would be over!!  Again the geneticist looked up at us and smiled,  "You have done a lot of our work for us.  That's how it's been since the beginning.  You even got yourselves genetic testing when we couldn't, and that's why you have answers. And you continue to do our work for us.  We've got some more things to look into."  I'm pretty sure I blushed.

Dr. V said, "Wow, we've got some things to do!  We've got some things to look into and a plan.  And the publication should come out this spring.  Often times with super rare syndromes like MN1 they will include the parents in writing the publication and list them as co-authors.  Given the cultural and language challenges, that may not happen here.  But they will send you a copy before it is published and they will want your input and suggestions for any changes or additions. They may want to add you as co-authors since you guys truly are the experts."  I couldn't believe all that I was hearing, all that was happening. After years of being questioned, discounted, and even accused of being crazy, as Jayson's parents we were instead being respected and referred to as experts.  

I asked what would happen after the research was published.  He explained, "At that point the literature will be changed to reflect that MN1 is a disease causing mutation and not one of unknown significance.  It will be given a name, sometimes using the first initials of the last names of the first kids involved in the study, other times after the researchers.  And then we hope for a treatment involving protein since this mutation involves the proteins."  I asked, "And that's where we as families work to fund research to work towards this treatment like through a foundation."  He added, "Yes, it's unlikely a clinician will want to invest in that research, but you never know.  They'll want to inject that same mutation into a mouse and study it, then add proteins into the DNA and see if we can improve the health of the mouse.  And then we work towards clinical trials with families, if the families are willing.  We often see families who are wanting to change their child's health conditions, but they don't want you changing the personalities of their child, which is a challenge.  They don't want you to completely change their child, which is a strange thing."  I had never thought of that before, and I laughed out loud.  I said, "Oh, I would be that parent.  I want my son's health to improve.  I want him to live a long, healthy life, but I love absolutely everything about him!  I wouldn't want you changing his personality either, which you're right, would be very hard if you are working on healing a child.  That will likely change their cognition and mannerisms.  Interesting."

We signed a consent to share Jayson's information and wrapped up our appointment.  The doctor sat thinking for a moment, then asked, "Remind me what each of you do for your careers?"  Mike shared that he's a city planner for Lehi and I shared that I train and support dual immersion teachers in the Granite School District.  He asked, "You're happy in your careers, I take it?  Helping people?"  "Yes," we both answered.  His next comment surprised me and made me smile, "Too bad.  I was hoping to recruit you to be nurses in our department."  What a compliment.  I can't think of a nicer thing for him to say.  He clearly supports and respects our family and our knowledge about our son and his medical conditions, which is so refreshing.

We walked out of our appointment overwhelmed and glowing.  We had a diagnosis.  Our son's medical conditions are mostly caused my a mutation found on MN1.  We know this now, and the research proving it will be published in 2017.  It's a dream come true.  Last year, Jayson and our family hoped and prayed for an answer for Christmas.  This year, we got it, and more!

As you can see, however, there are still a million questions.  How old are these other children?  What is the prognosis?  What are their health and developmental conditions and struggles?  What does their progress look like?  What can we expect?  Will there be a medical treatment?  How can we connect with these other families?  Are there others out there not yet diagnosed?  Are there any family members of these kids affected?  We don't know the answers to any of these, and we may not for some time, if ever.  A diagnosis when it is this rare does not give you much.  It tells us the exact gene that caused Jayson's syndrome, that is it.  It doesn't really give us answers, and it doesn't really help us with family planning.  It doesn't help doctors understand Jayson and his complex nature.  It doesn't tell us what to expect, what to watch for, what to worry about, what to let go, what he's capable of and what he's not.  It doesn't let us know how long he will live or what the major threats are to his health.  These were our main reasons for wanting a diagnosis.  We still know very little, which is frustrating.  But you have to start somewhere, and it ALL starts with a diagnosis.  Our very first appointment our geneticist told us only 50% of cases get diagnoses and what made me so certain we would be part of the 50% that get answers.  I told him that the 50% who didn't get answers didn't have me as a mother.  We are part of the 50% that got answers and I am proud to say that I've played an important role as Jayson's mother and advocate in getting us there.  I have fought for Jayson since day 1, and I won't stop now.  We need many more answers, and they will come.  Mike and I plan to work hard to find more families.  As we find more families, we get more answers.  We also plan to start a foundation once our syndrome or diagnosis gets a formal name.  Through the foundation we will hire a researcher, fund research, which will result in more answers and a treatment.  It will happen.  With time and collective effort, it will happen.  Jayson will change things, he already has.  Because of Jayson and his other 5 MN1 friends, things will be different for future MN1 families.  He's creating a legacy.  Amazing things will happen, even though we are at the ground level today.
It all starts somewhere, and fortunately for us, our newly-diagnosed story begins NOW.  
Thanks for being a part of it.  

Want to know how you can help?? Share our picture below and find us more MN1 families!  You can share our picture on Facebook or share THIS blog post from earlier this year with the picture.  Thank you so much for your love, encouragement, prayers and support that have got us to this point.  We are so very grateful!

All quotes are paraphrased from memories of actual conversations and not direct quotes.