(Title Image: Photo of Ava and I reading a book, coming off a strand of DNA)
Yesterday Ava had her annual physical exam at St Mary’s, Manchester Genetics department. Our old geneticist Dr Kingston had recently retired sadly, but we were transferred to the capable hands of her replacement Dr Browynn. Although we came out no further knowing Ava’s future, we came away with something we didn’t have before… HOPE.
The Back Story
|(IMAGE: Diagram showing the autosomal dominant inheritance pattern if one parent is affected. Showing 25% probability child will be affected)|
If you’re new to our journey, we attend St Mary’s because there was a risk of my children inheriting my Neuromuscular Disease, a rare Congenital Myopathy called Multiminicore Myopathy that there’s only 2,000 documented cases of worldwide. At the time of my unexpected pregnancy with my eldest Abbigail in 2012, the genetic cause of my muscle-wasting disease was unknown. With no known genetic cause means no way to test for it in utero. I was diagnosed age 3 1/2 years via muscle biopsy, so we have a definite diagnosis but an unknown cause. In 2004 TWO genetic mutations were discovered to cause Multiminicore Myopathy. SEPN1 that usually presents in a autosomal dominant pattern and RYR-1 which is usually recessive. Bloodwork was taken from me to test specifically for these two identified genes. Unfortunately 6 months later, the results raised more questions than they answered.
They expected me to have the RYR-1 gene mutation as we don’t know of anyone else in my family that presents with clinical markers for muscle disease. I tested negative for SEPN1 as expected, and the RYR-1 test came back INCONCLUSIVE. The way it was explained to me was that usually they see TWO mutations within the RYR-1 gene that brings about a congenital myopathy. They found ONE RYR-1 mutation in me. This ONE mutation could mean it took just one mutation within that gene to cause me to be like this or it could be a nothing. A mutation that doesn’t affect me at all. So it could mean everything or nothing.
Testing for RYR-1
It was decided as there was a 50‰ chance either way that it was viable to test Abbigail then 8 months old for RYR-1. Due to the condition having such a huge affect on a person’s life, it was important we knew as early as possible so IF (heaven forbid!) Abbie inherited this gene, we could prepare and get her the support and interventions she’d need from an early age. A further 6 months on, we got the results.
Abbigail did not inherit the RYR-1 gene!
A big sigh of relief that she would not have to endure what I did growing up with a muscle-wasting disease. Due to the fact it wasn’t directly passed on, Dr Kingston and her team determined my condition must be recessive, skip generations even and there was now a very small risk further children would inherit it.
Deciding to have Another Child
|(IMAGE: Left – Abbigail holding baby sister Ava for the first time in hospital. Right Ava, one month old sleeping wearing pink striped hoodie)|
With such reassurance and wanting to complete a family before my health deteriorated further, we decided to have another child.
Ava was born in 2012 and displayed odd symptoms at birth Dr’s couldn’t explain. Erratic heart rate, needing a feeding tube and jerky movements. She was released home under the care of the SCBU (Special Care Baby Unit) outreach team. Worried about these unexplained symptoms, we asked Dr Kingston to make sure Ava did not inherit this mysterious gene they found. Even though they thought as my eldest didn’t inherit it, the chances were very slim. Again at 8 months old, Ava had the relevant bloodwork.
Ava came back POSITIVE for the RYR-1 mutation.
They Were Wrong
|(IMAGE: Mum holding her head in her hands with the Quote; “When thinking about life remember this: no amount of guilt can solve the past. No amount of anxiety can change the the future”)|
I was devastated. I was angry. They’d told me it’d be so incredibly unlikely and we still didn’t know if this rogue RYR-1 meant a definite yes or no. Ava was examined by a Pediatric Neuromuscular specialist at 8 months and showed no hypotonia, failure-to-thrive or other trait of Multiminicore Myopathy normally seen in early infancy. It was reassuring, but knowing that gene was in her meant we’d have to come back YEAR after YEAR to have her looked over for signs. Multiminicore Myopathy is complex and just because I presented with symptoms from birth, doesn’t mean she will. It can show itself in childhood, adolescence or adulthood.
Every milestone was met not with joy but huge anxiety. Delayed motor milestones such as crawling or walking were traits. Ava didn’t walk until 17 months, compared to her big sister at 14 months. At 3 months old, she had a frightening experience where a simple cold turned into life threatening RSV and she ended up in HDU at our local hospital. Knowing full well that people with this condition develop significant progressive respiratory weakness and how many times I, myself have been hospitalised from the common cold, turn pneumonia practically overnight. Naturally I felt immense guilt and despair that my sweet baby girl was going through this and I blamed myself. Beat myself up, how I should of been more skeptical and not trusted our geneticists conclusion after our first child. I couldn’t turn back the clock, it was during that time I preparing to raise a child with a muscle-wasting disease while living with it myself.
–———— Bringing You Upto Date
|(IMAGE: Ava now 2yrs, in the play area at the genetics department)|
Back to yesterday’s appointment. I knew they’d need to hear from me how Ava has been doing since a year ago. Although Ava had some markers for the condition in infancy, after she finally got walking she has appeared incredibly strong (and strong willed!) in her limbs, enjoys climbing up anything and everything without any wobbles and has the type of endless energy you’d expect any “normal” 2 year old to have. So I explained it that way to Dr Browynn and asked her what her professional opinion was now.
The short answer is they still don’t know. There aren’t enough concrete clinical symptoms to say yes, she’s developed the condition but there’s some symptoms that make it so we can’t rule it out either. As she gets older it’ll become more clear.
The 100,000 Genome Project
|(IMAGE: Information poster about the project)|
After we’d established we were none the wiser and feeling the frustration and anxiety of this hanging over our heads possibly for years to come, Dr Browynn threw us an unexpected lifeline. Knowing my keenness for enrolling in any kind of research study to do with this condition, even if we don’t directly benefit from it, Dr Browynn handed me a leaflet about the 100,000 Genome Project.
I’d heard of this but naturally assumed it was for people who could afford to privately fund further genetic research. Dr Browynn went on to tell me that the NHS are putting 70,000 patients with rare diseases down for this project in a bid to find yet undiscovered genes. This project only applies to patients and families where exon sequencing and specific gene searches have drawn up blanks so have come to the end of the road. She thought our family would be perfect. I was gobsmacked and quite frankly felt extremely privileged and excited that we were even thought of. Now there was Hope!
The 100,000 genome project looks at a person’s entire genome for genetic mutations. It can take approx 2-5 years to fully analyse but we could potentially help scientists discover further mutations that cause Multiminicore Myopathy. Meaning other families wouldn’t need to go through the stress and frustration we have about not knowing. It could pave the way for further treatments aswell. Knowing the genetic cause would mean me and Ava would be allowed to participate in future clinical trials for treatments, which as it stands IF there was a trial… as it stands we wouldn’t be eligible as we don’t know the mutation involved.
|(IMAGE: Lab technician testing vials of blood)|
Those are the reasons why we stayed a further 2 hours for me to sign extensive paperwork and give further blood samples. I had to sign that agreed to let them continue to search for the gene, if I passed away before hand, for Ava’s and further patients sakes. That I understood that it may flag up other conditions I don’t know I have, but I’d only be told about the ones that have available treatments. If it was something that was incurable I’d need to pay if I really wanted to know. That my medical records will be shared with scientists all over the world, along with the other families enrolled. I’d be completely anonymous and just a case number. It was also important for me that I signed that Ava was not to be subjected to further testing until they found it in me.
For the first time in a long time, I came away from an appointment feeling like we stand a chance, that having such a rare disease doesn’t mean we will remain in the dark. Growing up having a condition like Multiminicore Myopathy, that is so incredibly rare means nobody but top researchers fight our corner, that we see people with more common conditions get treatments in their lifetimes, while we put on a smile and pretend to be hopeful the same will be said for us, but really the chances are slim to none. First we need to know what causes this, how it works exactly before any treatments can come about, so we are still in the very early stages of working out this disease. Not very encouraging for families just diagnosed. Now with the 100,000 genome project, a spotlight has been shone on rare conditions and that in itself is a dream come true.
And if because of this we find out for certain Ava has and will develop Multiminicore, I know that there’s a chance a treatment will be found in her lifetime, even if not in mine. Under the circumstances, that’s all I could ever ask for as a mother.