The photographs of Angus Powell when he was just six months old are joyful. His bright blue eyes, framed with long lashes, are full of curiosity and laughter.
And as far as his parents Oliver and Sophie were aware then, he was also completely healthy – if rather susceptible to more than his fair share of common colds and other bugs.
But it was around this time, without warning, that Angus suffered the first of what would become a seemingly endless string of terrifying seizures. And it was the beginning of a two-year nightmare for the family as they battled to understand what was happening to their precious boy.
The fits, which happened whenever Angus became ill, caused his limbs to twitch, his eyes to roll back in his head and his lips to turn blue.
They became progressively longer and more severe until, over Christmas last year, one set of prolonged convulsions led doctors to put the toddler into a medically induced coma for a couple of days to get them under control.
As the months rolled by it also became clear that Angus was lagging behind his peers when it came to speech and communication.
Former Welsh Guardsman Oliver – or Oli, as he’s better known – and Sophie, from Chaddleworth, Berkshire, were desperate for answers.
But despite scans and genetic tests, doctors had no idea what was wrong.
Three-year-old Angus Powell, pictured with mum Sophie, sister Lyla and dad Oli, carries a rare mutation in the CRELD1 gene. Only 29 people globally are known to have it
There was a chance Angus might become one of about 6,000 sick children every year who are told they have a SWAN condition – 'syndrome without a name’.
It’s not a diagnosis, but an umbrella term for illnesses believed to be genetic in origin but so rare doctors can’t pinpoint the precise cause.
And it’s a label that leaves families in a traumatic limbo – without any hope of treatment or cure.
In Angus’s case it was only because of the dogged determination of geneticists at John Radcliffe Hospital in Oxford that, in July, his illness was finally given a name.
The experts discovered that he, and a handful of others, carried a rare mutation in the CRELD1 gene. Only 29 people globally, including Angus, are known to have it.
The disorder it causes has now been named: Jeffries-Lakhani Neurodevelopmental Syndrome, or JELANS. Symptoms include seizures, heart and musculoskeletal issues, a weakened immune system, problems with vision and hearing, as well as cognitive delays and developmental issues.
Many of those affected have such serious health issues that they die very young.
Now three, Angus’s future remains far from certain, but Sophie and Oli were told his symptoms place him at the milder end of the scale, which has given them hope.
They are telling Angus’s story in the hope they can raise awareness not just of CRELD1, but of the families still in the dark about what’s wrong with their children.
To that end, Oli, 34, recently ran seven marathons in seven days for the charity Creld1 Warriors, raising more than £50,000 towards much-needed research into the condition.
Angus was around six months old when he suffered the first of what would become a seemingly endless string of terrifying seizures
Angus’s parents are telling his story in the hope they can raise awareness not just of CRELD1, but of the families still in the dark about what’s wrong with their children
Earlier this year the NHS approved Casgevy, a treatment for life-limiting genetic blood disorders once considered hopeless – sickle cell disease and beta thalassaemia. A similar gene therapy, Hemgenix, is offered to patients with the blood clotting disorder haemophilia.
These drugs cost upward of £1 million a dose – but just one dose is needed. And although it is early days, they appear to offer a cure.
If research moves in the right direction, the Powells are daring to dream of a similar breakthrough for JELANS. With better genetic testing, children could be treated before symptoms begin.
’The science is evolving so rapidly,’ says Sophie, 35, a former teacher. 'At the moment we don’t even have an effective treatment, but there may be a way with gene therapy. The hope could one day be a cure.
’We know how fortunate we are with Gus that we’ve been able to get a diagnosis. But there are other families still struggling and in the dark.
’They are in a far worse situation, in that they don’t have a diagnosis, or their child is suffering from far more severe symptoms.
’We want to make sure that we not only conduct far more research into this very rare condition, but that we make sure families like ours get the diagnosis they need to move forwards.’
Oli, who works for a renewable energy firm, and Sophie were delighted when Angus, their first child, was born without complications in June 2021. The first inkling anything was wrong came when he became ill with a lung infection when he was six months old and his temperature suddenly spiked.
’I laid him down on the bed to give him some Calpol and he started twitching,’ recalls Sophie.
’His eyes rolled back, his whole body was jerking. I couldn’t hear him breathe and his lips went blue. It went on for around five minutes – those minutes were absolutely terrifying.’
Paramedics said it was likely a febrile convulsion – a seizure which can happen when a child has a high temperature. But over the next three months, Angus had repeated throat and chest infections which triggered seizures.
’Doctors always reassured us he was fine,’ says Sophie. 'But when he was nine months old, and he had his first 45-minute seizure, they started thinking there was something more serious going on.’
On that occasion Angus was taken by ambulance to the John Radcliffe Hospital. 'I couldn’t watch – it was awful,’ says his mother. 'I kept asking the doctor, „Is he going to survive?” They just said, „We hope so.” You don’t want to hear that. It was very scary.’
An MRI scan and an EEG – a recording of brain activity – came back normal. Doctors considered he had a form of epilepsy and put him on drugs to control his seizures, with varying success.
’At the moment we don’t even have an effective treatment, but there may be a way with gene therapy,’ says Sophie
They also wanted to rule out a genetic cause, taking blood from Angus and his parents for an analysis of their DNA. But the CRELD1 mutation was so new it was not yet in the 'panel’ of faulty genes that scientists test for.
A Genomics England study is currently testing 100,000 newborns using a blood test that aims to screen for 200 genetic disorders before symptoms begin. CRELD1 is not yet part of this, but it is hoped it might be in future.
For Oli and Sophie it took a whole year for some initial results to come back, which found nothing. She had also given birth to their second child, Lyla, in August 2022, who did not have the same problems as Angus. 'It’s so hard not knowing what is wrong with your child,’ says Sophie.
Specialists vowed to perform more detailed genetic tests. In the meantime, Angus was still having seizures and falling behind on other developmental milestones.
’He had been crawling and walking as expected, but he wasn’t communicating. He wouldn’t understand simple things and would just blabber in his own way.
’We were hoping it was something he would grow out of, and that he’d miraculously catch up.’
Angus had his worst seizure just before Christmas last year. 'It was the last very bad one,’ Sophie recalls. 'The doctors put him into a coma because he couldn’t stop fitting. It was extremely scary. It was for a couple of days and we got out on Christmas Eve.
’We now have a medication, midazolam, which we give him straight away when he has a seizure.’
In July, the diagnosis finally arrived. They were told Angus had JELANS, the CRELD1 mutation – and quickly realised there was almost no research on it.
Sophie says: 'It raised more questions than answers. We found one medical paper about it. It had identified 18 children – and seven had passed away.
’I never thought I would come to any kind of acceptance about it. Every time I mentioned it, I’d just burst into tears.’
The couple sought opinions from neurologists, geneticists and other specialists, but all told them the same thing: no one had any real expertise in the condition and little was known of it.
What has helped has been finding Creld1 Warriors, which supports the handful of families dealing with the disease.
It was founded by Adam and Jessica Clatworthy, who lost their second child, Lola, to the condition aged two – before she was formally diagnosed. Their third child, Alfie, three, also has it.
’We’d been told Lola had a SWAN condition, and it was only when Adam posted a video online of her having a seizure that a woman in Canada said her symptoms sounded exactly like her daughter’s, who had passed away with a CRELD1 mutation,’ says Jessica. 'We asked our geneticist to test for it, but they refused as they couldn’t find information about it.
’But after Lola died, and Alfie started having similar seizures at just three months old, we asked them to test again for CRELD1. Within a few days, they’d found the mutation in that gene.’
Thanks to their perseverance, the CRELD1 mutation was added to the panel used by the NHS and Genomics England to test for genetic diseases in children having seizures – which is why Angus finally got his diagnosis.
Oli, far left, recently ran seven marathons in seven days for the charity Creld1 Warriors, raising more than £50,000 towards much-needed research into the condition
Dr Lucy Hanington, a geneticist at the Oxford Centre for Genomic Medicine, says: 'There are likely to be more children and adults living with what they think is epilepsy or developmental delay when it could be a CRELD1-related disorder.’
Oli says being in touch with the charity, and with the other families from the US, Germany and Canada who have experience of the disease, has been 'inspiring’.
’It gave us hope,’ he says. 'They have stories of children who, despite health issues, are living pretty happy and normal lives.’
The funds from Oli’s marathons will help pay for a researcher, Birmingham University neuroscientist Dr Felix Chan, to investigate the condition.
’Angus is a happy little boy who loves running around outside and is always getting up to mischief,’ says Sophie. 'But his delayed development and lack of speech and communication can be challenging. And we don’t know how his condition will manifest as he gets older, which is scary.’
One positive postscript of Angus’ diagnosis is that Sophie, five months pregnant with the couple’s third child, was able to have her baby tested in the womb for JELANS.
She’s due in April – and the baby has been given the all-clear.
- Donate to Oli and Sophie’s fundraiser for Creld1 Warriors – visit justgiving.com and search CRELD1. More information at creld1.com
DNA editing at £1m a dose
FOR those with serious genetic illnesses there was once little hope.
However, a wave of new drugs that can rewrite DNA are transforming treatment – and have already thrown a lifeline to patients with conditions such as haemophilia and sickle cell disease.
Called clustered regularly interspaced short palindromic repeats, or CRISPR for short, they can correct minute errors in DNA, effectively offering a cure for genetic problems in a single dose.
Using a breakthrough technique, a harmless virus can be programmed to seek out the faulty DNA strands and deliver the CRISPR medication.
This gene editing technology is often likened to a pair of molecular scissors that can seek out a specific strand of DNA and snip pieces off. However they must be perfectly tailored to each patient’s genetic make-up, making them incredibly expensive to make – the single dose can often cost more than £1 million.
Despite this, for many they hold the only hope for recovery, and more than 150 trials are currently using the technology to treat conditions ranging from hereditary heart disease to eye deterioration.
