Ring Chromosome 20 Syndrome, or (R)20, is an ultra-rare form of epilepsy with a devastating impact – yet despite huge leaps forward in gene sequencing in recent years, diagnoses are going down instead of up. We spoke to Allison Watson, co-founder of Ring 20 Research and Support, about raising awareness, building the evidence base, and the importance of helping people through a pandemic despite limited funding.
Allison’s son David was just six when he started displaying the symptoms of (R)20, a genetic condition that can cause multiple, uncontrollable seizures, declines in cognition and mobility, and terrifying hallucinations.
As with many cases of (R)20, often called ring 20, David’s seizures appeared to come out of the blue.
“Unlike with many similar conditions, a child will develop normally until the seizures start to kick in,” said Allison.
“The child will often go backwards and lose abilities that they previously had. They may lose the ability to process properly or to speak. They might lose mobility and need a wheelchair. Others need help feeding.”
Ring 20 is a chromosome anomaly. Instead of being a pair that looks like two sticks, one or both arms of the 20th chromosome are joined at the ends, making them look like a ring under the microscope.
“A lack of awareness of the condition, which is known to affect at least 150 people worldwide, contributes to a diagnostic delay, said Allison, adding that children often experienced nocturnal, hallucinogenic seizures that healthcare professionals were simply not familiar with.”
The resulting seizures vary – in length, type, and severity – from person to person, but even mild forms of the disease have a huge impact on quality of life.
Typically, people have impaired awareness seizures that can last anywhere between 20 and 40 minutes. For some, this can go on for days, leaving them in hospital or even in an induced coma.
“My son, who is now 23, will have four to six non-convulsive events every day – that’s just normal.
“It’s like the lights are on but no one is home, so you have to be really careful. They could be doing something like cooking or having a bath. It really impedes their independence,” said Allison.
Non-existent treatments and diagnostic challenges
Despite the huge unmet need, ring 20 diagnosis is slow, and treatments are practically non-existent.
“Ring 20 doesn’t respond to any treatments: nothing seems to work. There are no clinical practice guidelines, meaning doctors treat on a case-by-case basis. They are effectively working blind,” said Allison, who co-founded the charity in 2014.
“Families just have to learn to live with these regular seizures and the associated comorbidities.”
A lack of awareness of the condition, which is known to affect at least 150 people worldwide, contributes to a diagnostic delay, said Allison, adding that children often experienced nocturnal, hallucinogenic seizures that healthcare professionals were simply not familiar with.
“A child may appear to awake from sleep. They may shake or shout out and can have a stiffness in their bodies or their arms. They may have a frightened expression on their face, and some describe horrific events. They see sharks swimming around their head, or fire in the room, or big black holes jumping up in front of them.
“This is often misdiagnosed and disregarded as night terrors, so this obviously denies diagnosis.”
Another, apparently contradictory, point is that the number of ring 20 diagnoses have actually declined with advances in genome sequencing, which cannot detect the presence of ring chromosomes.
Allison explained: “Human genome sequencing, exome sequencing, and even CGH array all look for additions, duplications, or something missing from the DNA. But in the majority of ring 20 cases, there is no misspelling in the chromosome.
“The way to diagnose it is to go back to the old-fashioned carrier type, to physically look at the cells under a microscope to see the rings.”
Additionally, doctors looking for a chromosome abnormality would typically send 30 cells for analysis. But the misshaped chromosomes that characterise ring 20 are only present in a certain proportion of the person’s cells.
Said Allison: “They need to be sending about 100 cells for analysis, otherwise they could miss the ring.
“We suspect that this particular disease is very underdiagnosed in people with genetic epilepsies or an undiagnosed cause for epilepsy, and we also suspect that people that do have a diagnosis may be potentially misdiagnosed.”
Raising awareness, offering support
That’s why Allison is so keen to build the evidence base and raise awareness of the condition.
As co-chair for EpiCARE, the European Reference Network for rare and complex epilepsies, she is working on projects ranging from a patient pathway map to e-learning modules for healthcare professionals.
And members of Ring 20 Research and Support have raised enough money to embark on a two-year natural history and biomarker study, as well as establish a patient registry.
“This is a fundamental building block to future research opportunities so we’re very proud of our families for getting us to this point,” she said, adding that the registry “would have been up and running by now if it wasn’t for COVID”.
The pandemic caused both a surge in demand and a drop-in financial support – a problem that has been seen across the patient support sector.
But with it being more important than ever to ensure people with ring 20 and their families get the support they need, so COVID or no-COVID, Allison and her team have no intention of scaling back their plans. In fact, they have even extended their offering to include online peer networking.
“Because our families are so disparately located, some may never get to meet another family with ring 20 at all. So, we have been having fortnightly Zoom calls. We’re connecting families from the US and Australia, the UK and Europe, even South Africa,” said Allison.
“We’re based in the UK, but we support families worldwide. We’re the only organization doing this,” said Allison.