Global genomic collaboration improves lives and treatment for children with epilepsy

17 Aug 2023, 8 a.m.


An international research collaboration, including GOSH and our research partner UCL Institute of Child Health, has shown that a technique known as rapid genome sequencing can provide a diagnosis for 43 per cent of children with unexplained epilepsy and significantly benefit their care. 

Please note this article includes a story that covers the topic of baby loss.

Epilepsy in children ranges in severity and can leave families and carers with many questions about their child’s future health. While genetic testing to find the cause of epilepsy is possible it can take a long time, leaving families waiting for answers.

Published in The Lancet Neurology today, this international study sequenced the genomes of 100 babies under the age of one with unexplained seizures from four countries (England, USA, Canada and Australia) to better understand the potential strengths of early, broad genome sequencing (a process which looks for changes across the entire genome) for infantile epilepsy.

The researchers used rapid genome sequencing (rGS) to investigate the impact of an expedited genetic diagnosis on care for the first time. Across all children enrolled in the study, 43 per cent received a diagnosis within weeks, and that diagnosis impacted prognosis in nearly 90 per cent of those cases, guiding treatment options for over half.

Called Gene-STEPS, Shortening Time of Evaluation in Paediatric epilepsy Services, the study is the first collaboration launched through the International Precision Child Health Partnership (IPCHiP), an international consortium (Boston Children’s Hospital, Murdoch Children’s Research Institute with The Royal Children’s Hospital, The Hospital for Sick Children (SickKids) and UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) and Great Ormond Street Hospital) that leverages each institution’s expertise and genomic infrastructure to accelerate discovery and the development of therapies for children.

The UK team, led by Dr Amy McTague (GOSH and UCL GOS ICH) utilised expertise within the Translational Research Team at the North Thames Genomics Laboratory Hub (NT GLH) to establish a new rGS pathway for children enrolled in the study at GOSH.

Amy McTague stands in a black t-shirt and white lab coat. She has her arms crossed and is smiling at the camera, she has a short dark brown bob.

Dr Amy McTague, UK study lead, honorary consultant paediatric neurologist at GOSH and clinician scientist at UCL GOS ICH

It’s incredibly exciting to share the results from the first phase of this IPCHiP project and, importantly, it is fantastic that this research has provided powerful evidence for the clinical benefits of rapid genomic sequencing in young children with new-onset epilepsy.

Through a global collaboration of expert researchers, we have shown how this testing can be used, across four different healthcare systems, to rapidly diagnose children with epilepsy, finding an answer in over 40% and guiding treatment in over 50% of these children. This has the potential to impact many families across the world and provide much needed information to clinical teams in charge of their care. We are incredibly grateful to every family that took part in this study, research like this is only possible because of them.

Dr Amy McTague, UK study lead, honorary consultant paediatric neurologist at GOSH and clinician scientist at UCL GOS ICH

Genetic insights inform clinical care

Currently, there are more than 800 known different 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 may explain a medical condition, analysing the entire genome.

The UK arm of the study was part-funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity) and the National Institute for Health and Care Research (NIHR) GOSH Biomedical Research Centre with support from Young Epilepsy. The collaboration utilised expertise and infrastructure from the Translational Research team at the NT GLH as well as data teams from within the GOSH Digital Research Environment to rapidly develop a rGS pathway within an established clinical genomics facility.

This powerful in-house sequencing technique allowed researchers to not only provide a rapid diagnosis for many families, but also had an immediate impact on clinical care – allowing for faster access to correct treatments, fully-informed decision making and often further clinical investigations.

In this study, both biological parents and the child underwent rGS, known as ‘trio’ sequencing, to more quickly understand whether gene changes in the children were inherited or new to the child (de novo). These insights are important for families to understand how the results impact their lives and their plans for any future children.

Family impact

Please note this story covers the topic of baby loss

Leo Bush was born prematurely on the 24 October 2021, and, despite early positive signs, he rapidly began to develop serious symptoms including seizures. Despite lots of invasive testing and attempted treatments, doctors struggled to understand what was wrong with Leo. At six weeks old he was transferred to GOSH for specialist treatment and almost immediately enrolled in the IPCHiP study.

Leo wears a white beanie and sucks his thumb. He has a feeding tube attached with bear tape.

Approximately two weeks after giving samples of their blood for testing, the family were told that Leo had a very rare genetic diagnosis of BRAT1-related neurodevelopmental disorder caused by inheriting a faulty copy of the gene from both his parents. The mutation causes a very severe form of intractable epilepsy in children. There is currently no treatment for the condition and management of symptoms is incredibly difficult. Babies with this genetic epilepsy rarely survive beyond first six months of life.

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

It was completely and utterly heart-breaking but getting a diagnosis provided us with a reason. 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

Andy, Leo's Dad

We really want to build the understanding people have of how powerful a genetic diagnosis can be. 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.

Sofie, Leo's Mum

Andy and Sofie have 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. 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.

Andy, Leo's Dad

Building on research

The international research team is continuing to follow-up with clinicians and study participants to understand how rGS has influenced children’s development long-term. The GOSH team are also hoping that they will be able to bring this test into clinical service, giving families across the country access.

The results published today highlight how this worldwide collaboration is already enabling us to combine collective knowledge and research expertise to benefit children around the world. Through support in the UK from the NIHR GOSH Biomedical Research Centre and GOSH Charity, we have been able to demonstrate the power that rapid genetic sequencing can have for children with epilepsy. Embedding research into all aspects of care at GOSH, through the partnership with the UCL Great Ormond Street Institute of Child Health, enables studies such as this one to bring cutting-edge technology and developments into clinical practise.

Professor Helen Cross, Director of the UCL GOS ICH, Honorary consultant in paediatric neurology at GOSH and investigator on the project

This study was funded by the American Academy of Pediatrics, Boston Children’s Hospital Children’s Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Children’s Charity, Medical Research Council, Murdoch Children’s Research Institute, National Institute of Child Health and Human Development, NIHR Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, and University of Toronto McLaughlin Centre.

This paper highlights the impact that funding translational research and international collaborations can have on families and our clinical practice. At the NIHR GOSH BRC we are proud to continue to support research through the North Thames Genomics Laboratory Hub to understand how integrating rapid genetic testing into routine care can benefit families around England.

Professor Thomas Voit, Director of the NIHR GOSH BRC

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. 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.

Dr Kiki Syrad, Director of Impact and Charitable Programmes at GOSH Charity

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