Genomics will revolutionise treatment for childhood rare diseases

A global study has proven the power of a simple genomics blood test to improve treatment and care for childhood epilepsy, but more investment is needed to make access fair and securely join up the data to treat more rare diseases.

The International Precision Child Health Partnership (IPCHiP), which is a collaboration between UCL and Great Ormond Street Hospital, the Murdoch Children’s Research Institute (MCRI) in Australia, and The Hospital for Sick Children (SickKids) (Toronto) and Boston Children’s Hospital, has shown that rapid genomic sequencing can revolutionise care for children with rare diseases – changing and improving diagnoses, changing treatment plans and allowing patients, families and doctors to make more informed decisions.

Many childhood epilepsies are genetic in cause and, with over 1,000 epilepsy genes identified, knowing which genetic variants are responsible for a child’s epilepsy, or if there is no known genetic component, can help to guide treatment and care. Early detection and diagnosis is important to support children and families as early as possible.

Gene-STEPS, the first project from IPCHiP, explored the use of rapid genome sequencing (rGS) for children with newly-diagnosed epilepsy. The teams found that not only was rGS feasible across four different countries and health systems from a standard blood test, it provided a genetic diagnosis for 43% of children in under three weeks. Importantly, for 98% of children with a genetic diagnosis there was a significant impact on their treatment, such as choice of antiseizure medication.

These most recent results from IPCHiP will be published in npj Genomic Medicine for Rare Disease Day 2025, where the urgent need to step up efforts to advance genomic diagnosis and precision treatment for rare childhood conditions was a focus.

Sarah’s daughter was just three months old when her seizures started. When scans ruled out other causes, they were told the answers could be in her genetics. Without this research project, Sara and her family would have had to wait many months for genomic investigations.

“We were so worried as she was our first baby and it was all so new. Taking part in research meant that in three weeks we had the answers we wanted. Our little girl’s epilepsy is genetic and the doctors were able to confirm that the treatment she was on was the best one for her and adjust the dose to be even better.

“As her genetic variation is so rare – she’s 1 of just 10 known cases in the world – there isn’t much information out there about what we can expect. We

were so lucky to be at GOSH but this needs to be available to all parents, regardless of where they live or if they can afford to pay privately.

“Most people who know us don’t know our little girl has epilepsy – there is still such a stigma attached to what she may or may not be able to do.

“Even if the genetic diagnosis doesn’t change anything for the child or the family, just recording more genetic causes and cases so that we know we are not alone and have some idea of what might be ahead for us, would be a huge benefit.”

“Having clarity around our chances of having a child with another genetic variation allowed us to receive genetic counselling and quickly make plans to grow our family with support from genomic experts.”

Dr Amy McTague, lead investigator from the UK partner, Great Ormond Street Hospital and UCL Great Ormond Street Institute of Child Health said: “It was fantastic to see that we could so quickly advance precision child health in this way in our pilot project. We have learnt a great deal from this process about international collaboration and the need for wholesale adoption of this into clinical care.

“Money spent on child health pays dividends, not just in quality of life for our young people and their families, but in creating a happier and healthier population and communities for the future.”

Professor Dame Lyn Chitty, Deputy Director of the NIHR GOSH Biomedical Research Centre and lead of their Genomic Medicine Theme said: “This work has shown the power of collaborative research in rare conditions to test and learn from genomics. We now need the data infrastructure to extend this research to other conditions to enable more people access to these advances in genomics. For that to happen, we urgently need investment in informatics and governance to enable data sharing whilst protecting patient confidentiality.

Professor Helen Cross, Director of the UCL Great Ormond Street Institute of Chid Health and co-author of the study said: “This study really demonstrates the power of specialist collaboration. Genomics is providing answers in many rare diseases and changing our approach to treatment. Coming together enables us to test the benefits of treatment in a feasible way, and hopefully result in better outcomes.”

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.

Aoife Regan, Director of Impact and Charitable Programmes at GOSH Charity said: It's incredibly exciting to see the power of genetic sequencing in improving treatment and care for childhood rare diseases. We are proud to support this research, and consider it an excellent example of the importance of global collaboration and working in partnership to accelerate the breakthroughs of tomorrow and transform the lives of seriously ill children across the world.

When combined, rare diseases affect 1 in 17 people and, collectively, are not particularly rare. Improving the health of those affected by a rare disease is a major global challenge but one that has the potential to be revolutionised by genomics technologies. Genomic screening can improve the understanding and burden of a disease, its underlying causes and help clinical teams decide on the best treatments for success or avoid harsh treatments that the genome tells us will not work or be tolerated. This is called precision medicine.

The next stage of IPCHiP will explore use of similar sequencing for infantile hypotonia in a project called GemStones, run by Dr Giovanni Baranello at Great Ormond Street Hospital. GemStones will explore the utility of genomic screening to improve access to a more accurate diagnosis that isn’t currently available in standard-of-care.

The IPCHiP partnership prioritises collaboration and shares innovation across four leading paediatric institutions that incorporate research into all they do. The establishment of rGS across four different healthcare systems required commitment from each institution and their supporting genomics services. The IPCHiP team are now working together to use innovative approaches to data sharing to ensure patient data is kept safe and secure but learnings from these rare patient cohorts can be shared across continents.