Genomics to revolutionize treatment of childhood rare diseases

The International Precision Child Health Partnership (IPCHiP), operating at sites across the UK, Canada, the US and Australia, has shown that rapid genomic sequencing (rGS) can revolutionise care for children with rare diseases. It can improve diagnoses, enhance treatment plans and allows patients, families and doctors to make more informed decisions.

Rapid genome sequencing is a technique that quickly reads and analyses a person’s genetic material by breaking it into small fragments and sequencing them all at once.

Many childhood epilepsies are caused by genetics. With over 1,000 epilepsy genes identified, knowing which (if any) genetic variants are responsible for a child’s epilepsy can help to guide treatment and care.

Early detection and diagnosis are important to support children and families as early as possible.

The results from Gene-STEPS, the first project from IPCHiP, are published in npj Genomic Medicine and explore the use of rGS for children with newly-diagnosed epilepsy.

The teams found that not only was rGS feasible from a standard blood test across the four countries’ different health systems, it also 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 a choice of antiseizure medication.

Lead investigator from the UK partner, Dr Amy McTague (UCL Great Ormond Street Institute of Child Health and GOSH) 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, of the UCL Great Ormond Street Institute of Child Health and Deputy Director of the NIHR GOSH Biomedical Research Centre, 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 Child Health and co-author of the study added: “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.”

When combined, rare diseases affect one in 17 people. 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 won’t be tolerated. This is called precision medicine.

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.”

The next stage of IPCHiP will explore use of similar sequencing for infantile hypotonia (a condition where a baby has unusually low muscle tone, making them appear limp or floppy) in a project called GemStones, run by Dr Giovanni Baranello at GOSH.

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.

IPCHiP is a collaboration between UCL and GOSH, the Murdoch Children’s Research Institute with The Royal Children’s Hospital (Melbourne Children’s Campus) and the University of Melbourne Department of Paediatrics (Melbourne), and The Hospital for Sick Children (SickKids) in Toronto and Boston Children’s Hospital.

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 (BRC) with support from Young Epilepsy.