Research supported by GOSH Charity improves diagnosis for children with epilepsy

17 Aug 2023, 2:15 p.m.

Baby Leo swaddled in a blanket

Please note this article covers the topic of baby loss.

Baby Leo sadly passed away when he was just a few months old. Getting a diagnosis at GOSH, made possible thanks to an international research project, provided solace to his parents at an extremely difficult time.

Leo was transferred to GOSH for specialist treatment when he was six weeks old, after developing a range of symptoms including seizures. Despite many invasive tests and attempted treatments, doctors had struggled to understand what was happening.

“That period was so incredibly stressful, there was so much uncertainty and we just wanted to try everything possible to understand what was wrong with Leo,” says Leo’s mum, Sofie. “Everyone assumed it was something Leo had acquired, no one ever considered it was something genetic.”

At GOSH, Leo was enrolled in Gene-STEPS, an international research study that used rapid genome sequencing to investigate the impact of a quicker diagnosis for babies with suspected genetic epilepsy. Genetic testing to find the cause of epilepsy isn't new, but it often takes a long time, leaving families waiting for answers.

As part of the study, researchers sequenced the genomes of 100 babies under the age of one across England, the US, Canada and Australia. Of all the children enrolled in the Gene-STEPS study, 43% received a diagnosis within weeks, and this diagnosis helped guide treatment options for more than half.

Receiving a diagnosis

To run the rapid genomic sequencing for Leo, teams at GOSH collected blood samples from Leo, Sofie and Leo’s dad, Andy. About two weeks later, they were told he had a very severe form of intractable epilepsy, caused by inheriting a faulty copy of the BRAT1 gene from both his parents. There is currently no treatment for the condition and management of symptoms is incredibly difficult. Babies with this genetic epilepsy rarely survive beyond the first six months of life.

Leo was 79 days old when he passed away in Andy and Sofie’s arms on 10 January 2022.

“It was completely and utterly heartbreaking, but getting a diagnosis provided us with a reason,” Andy says. “It allowed us to start processing. The diagnosis made an impossible situation easier. We may not ever find a cure for BRAT1, but having a diagnosis – an answer – was, for us, so powerful.”

Creating a community

Having a diagnosis for Leo helped Sofie and Andy to build a community. They established a group for other families who had children with a BRAT1 diagnosis, finding support among others who are connected to the incredibly rare condition. They have also set up a Brighter Future Fund in Leo’s memory to raise money for the research that provided them with Leo's diagnosis.

“We really want to build the understanding people have of how powerful a genetic diagnosis can be,” Sofie says. “We also know how lucky we were to be at GOSH and be part of this research project – we desperately want to see tests like this rolled out more widely so that everyone has the access we did.

“The test was so simple – just a blood test. After so many invasive procedures that provided no answers, it was so powerful to us that the information we needed came from a simple blood test for Leo.”

Andy and Sofie recently welcomed a baby daughter into the world and are enjoying their time together as a family.

“This is yet another reason that a diagnosis for Leo was so powerful for us,” Andy says. “It didn’t just allow us to process and work through our grief, but it has also given us the chance to build our family.

“Unfortunately, there is a one in four chance of our children inheriting the same condition as Leo, but because we know the specific gene mutation we can test at a relatively early stage in pregnancy. As a result, fortunately we know our daughter is a carrier (like both her mum and dad) but does not have the condition. That makes an enormous difference.”

A global collaboration

Gene-STEPS, the study Leo was part of, was the first collaboration launched through the International Precision Child Health Partnership (IPCHiP). This is an international consortium including GOSH, the UCL Great Ormond Street Institute of Child Health (UCL GOS ICH), Boston Children’s Hospital, The Hospital for Sick Kids and the Murdoch Children’s Research Institute with The Royal Children's Hospital.

IPCHiP leverages each institution’s expertise and genomic infrastructure to speed up the discovery and development of therapies for children.

The UK arm of Gene-STEPS was part-funded by GOSH Charity, along with the National Institute for Health and Care Research GOSH Biomedical Research Centre with support from Young Epilepsy.

Dr Kiki Syrad, Director of Impact and Charitable Programmes at GOSH Charity, says the research shows the powerful potential of global collaboration.

“We know that early diagnosis of rare conditions is so important, and it is incredibly exciting to see the difference that genetic sequencing has made to the patients and families taking part in this study,” she says.

“This research is a fantastic example of what can be achieved through international collaboration and funding partnerships which support pioneering researchers seeking the breakthroughs that will transform lives.”

Next steps

There are more than 800 known genetic causes of infantile epilepsy, and many have similar symptoms during early childhood. Unlike more targeted genetic testing that is often used to confirm a suspected diagnosis, genome sequencing looks for any changes in a person’s DNA that might explain a medical condition.

The UK team, led by Dr Amy McTague, honorary consultant paediatric neurologist at GOSH and clinician scientist at UCL GOS ICH, worked with the Translational Research Team at the North Thames Genomics Laboratory Hub (NT GLH) to establish a new rapid genomic sequencing pathway for children enrolled in the study at GOSH.

Providing a rapid diagnosis for families had an immediate impact on children's care, allowing for faster access to correct treatments, fully informed decision making and further clinical investigation.

"This has the potential to impact many families across the world and provide much needed information to clinical teams in charge of their care,” Dr McTague says. “We are incredibly grateful to every family that took part in this study, research like this is only possible because of them.”

In future, the GOSH team hopes to bring the test into clinical service so families across the country have access to it.

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