Abstract
Adam Clatworthy, a communications professional at a technology firm, talks about the importance of parents and patients – who are experts in the complex conditions and symptoms of rare diseases that they live with – working together with clinicians to help deliver diagnoses.
Please would it be possible to introduce yourself, your family & your story
We are the Clatworthy family and we live in Hampshire in the UK. My wife Jess is a paediatric nurse and I work in corporate communications. We are parents to three wonderful children – Daisy (7), Alfie (1) and Lola who is sadly no longer with us.
We first heard about CRELD1 when our daughter Lola started having frequent seizures at just 3 months old. Lola had severe developmental delay, was struggling with feeding and mobility and often experienced upwards of 80–100 myoclonic twitches and prolonged seizures every day. By pure chance, a mother in one of the epilepsy Facebook groups recognised Lola’s seizures from those that her son was having.
We quickly established many similarities in our children’s symptoms and experiences. This proved to be a far more reliable source of intel than what we gathered from the geneticists who initially brushed off our suggestions saying, “We’ve not seen any links between epilepsy and CRELD1, so it’s highly unlikely to be that…” This was one of the big issues-no-one believed me that it could be CRELD1, and they wouldn’t test for it. This made us feel like we didn’t know what we were talking about because we’re ‘just parents’. We kept talking to Katie, convinced there was a link, but we continued with our investigations into Lola’s struggles.
A few weeks before Lola’s third birthday, and just 4 days after her little brother Alfie was born, our worst nightmare became a reality when we tragically lost Lola, peacefully in her sleep. Her cause of death was put down to Sudden Unexpected Death in Epilepsy (SUDEP), a tragic outcome for many children diagnosed with severe epilepsy.
We quickly learnt that this wasn’t the end of our nightmare, as her brother Alfie started having the same seizures at 3 months old. We flagged to our geneticists again, so they reanalysed her DNA sample and we soon had confirmation that Lola did indeed have sequence changes in the CRELD1 gene that had caused an extremely rare genetic disorder. Alfie was then tested and also diagnosed with the same CRELD1 gene sequence variation.
While this diagnosis has simply turned our lives upside down, we have found an incredible community of inspirational families from across the USA, Canada and UK that are all caring for children with CRELD1. These families give us hope, ideas, love and support as we all fight this together.
What information & research is available for CRELD1-related disorders?
If you Google ‘CRELD1 and epilepsy’, very little comes up in the search, which means that any parents faced with the same condition are completely lost when given this extremely rare diagnosis.
I have spent the last 4 years searching for guidance, answers and support to help families firstly recognise, and then deal with this ever-challenging condition. The only mention of epilepsy and CRELD1 is a publication that discusses precision medicine and COVID-19, where a person with CRELD1 and seizures is mentioned in passing.
Over the last 4 years, we have worked alongside Yale University School of Medicine to draft the world’s first CRELD1 medical literature – pre-proof version has since been published.
We have also helped get CRELD1 added to the Genomics England PanelApp and secured a license for pre-natal testing of CRELD1 for other families.
Where can families with a child suffering from a CRELD1-related disorder find support?
Less than 20 children have been diagnosed with CRELD1 around the world, so when we talk about this being a rare disease, we are, in scientific terms, talking about something that is extremely rare. Through social media we have created a group that has been a lifeline to us, and others faced with the challenges CRELD1 brings. This group is now part of our new extended family, helping us all learn as much as possible. We all talk almost every day and share key learnings about our children’s symptoms and different tests/learnings that have then helped us all.
Sharing these experiences led me to creating the CRELD1 Warriors website – a place where other families could find comfort in being connected, where they weren’t alone, and where they had a chance to learn from the experiences we had all been through.
Now, if you Google ‘CRELD1 and epilepsy’, our website is the first site you’ll see. Since launching the site last August we’ve had over 3000 unique visitors and we’ve heard directly from families in the UK and in the US that got a CRELD1 diagnosis for their children – simply by finding the website.
What is the mission of CRELD1 Warriors?
Our mission is straightforward: we want to raise awareness of CRELD1, support medial research and provide support for families caring for anyone with CRELD1.
When you think about how much time a doctor, neurologist or geneticist can physically spend with a patient, there is no way that they can fully understand their complex condition or symptoms. We often don’t have the academic or scientific background, but as parents we live with and learn from our children every second of every day. The website is our way of ensuring that we share our key knowledge and experiences, ultimately ensuring that no-one suffering from this condition feels alone.
Can you share from your own experiences some of the challenges that parents of children with a CRELD1-related disorder encounter when trying to find a diagnosis & treatment
The most common characteristics found in the children diagnosed with CRELD1 is intractable seizures and varying developmental delay, which is why it has proven so difficult to identify effective treatments.
The battle we face is one of bringing the scientific and parent community together, to form a network of individuals that are all going through the same challenges, helping us focus on identifying the right treatment options, rather than testing multiple drugs that we have no idea will work and bring many damaging side effects.
It also means that that we can help make the connections and ensure that the UK and USA can learn from each other and share information with families with other potentially undiagnosed children suffering the same challenges across the world.
Earlier this month I had the privilege of sharing our experience with NHS nurses, clinicians, neurologists and midwives at the South East Genomics Epilepsy & Genetics event in London. Bringing this community together to advance awareness and understanding is something we will continue to do. CRELD1 Warriors has since been added to UK Rare Epilepsies Together (UKRET) so that we can be recognised alongside other rare epilepsies and have a voice among this vital community.
Over the coming years, how do you see these challenges changing?
International collaborative research is underway, and researchers from Yale School of Medicine will soon be publishing its scientific paper linking a number of children with similar symptoms and genetic results. Two rare genetic changes have been detected within the gene on chromosome 3 and are considered disease-causing. The gene changes have been found in both parents and therefore the chance of having another affected child is 25%.
This paper is vital in ensuring that CRELD1 is recognised by the medical community as a genetic variation of significance, and will be included in any genetics testing moving forward, such as the NHS National Genomic Test Directory, as well as the virtual gene panels that were used in the 100,000 Genomes Project.
And while in the long-term, these steps are hugely encouraging, as a parent you have to look at the short-term as well as the longer-term options available-in a sense, you’re prepared to leave no stone unturned. The focus now needs to be on identifying potential treatment options to help provide seizure management and the best quality of life possible for our CRELD1 children.
Do you have any final comments or useful resources for the readers of Future Rare Diseases?
Since we started our CRELD1 journey over 4 years ago we have been blessed to find a small community of families that have had their children diagnosed with the same condition. While CRELD1 is extremely rare – we want to encourage families to share their story and create a place where they can find relevant information. You can find further reading here: https://www.creld1.com
Financial disclosure
The author has no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
Interview disclosure
The opinions expressed in this interview are those of Adam Clatworthy and do not necessarily reflect the views of Future Medicine Ltd.
Competing interests disclosure
The author has no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.