Global genomic collaboration improves lives and treatment for children with epilepsy

An international research collaboration, including Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH) and 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. 

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, 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.

Genetic insights inform clinical care. 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.

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 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.

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

“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."