Transforming clinical care for children with rare genetic diseases

Global partnerships that embed scientific research into clinical care are revolutionising the diagnosis and treatments for children with rare genetic diseases, according to a new report.

The white paper found despite advances in genomic technologies, which can detect rare genetic diseases within days, there remained significant challenges to ensuring this leads to improved child health outcomes. But global collaborations, such as the International Precision Child Health Partnership (IPCHiP), using evidence-based approaches to inform decisions in real-time, are overhauling patient care.

The paper was led by Murdoch Children’s Research Institute (MCRI), The Hospital for Sick Children (SickKids), Boston Children's Hospital, UCL Great Ormond Street Institute for Child Health (GOS ICH) and Great Ormond Street Hospital (GOSH).

Rare diseases are becoming increasingly common affecting about 300 million people globally. One in three children with a rare disease will die before the age of five.  

MCRI Dr Katherine Howell said identifying a genetic diagnosis was the first step in delivering precision medicine.

More than 70 per cent of rare diseases, now totalling up to 10,000, have a genetic cause.

“Advances in genomic technologies, especially exome sequencing and genome sequencing, and integrating these tests into clinical settings have considerably improved diagnostic yields for rare diseases,” Dr Howell said.

“A genetic diagnosis often informs clinical management, treatment, prognosis and access to resources and support. Over 600 rare disease genes that often emerge in childhood and cause severe disorders have treatment available, underscoring the urgency for improving diagnosis rates.”

The report, published in npj Genomic Medicine on Rare Diseases Day, found with limited and often inequitable access to genomic testing, wide-sweeping international efforts were needed to accelerate accurate diagnosis and implement evidence-based practice changes.

“A coordinated approach on a global scale can energise collaboration and maximise research output by building on the diverse expertise and existing efforts, reducing duplication and creating frameworks for responsible data collection and sharing,” Dr Howell said.

“Multidisciplinary collaborations are also required to connect clinicians with scientists to advance our understanding of diseases and forge partnerships with industry, foundations, and patient advocacy groups to identify opportunities for development of new therapies and rapidly translate them to the clinic.”

IPCHiP, an international consortium leveraging the medical and scientific expertise from MCRI, SickKids, Boston Children's Hospital, GOS ICH and GOSH aims to use genomic data to accelerate discovery and therapeutic options. It has recently been designated a ‘Driver Project’ of the Global Alliance for Genomics and Health (GA4GH).

SickKids Professor Stephen Scherer said by embedding research in clinical practice, IPCHiP was generating the evidence and model needed to advance precision medicine.

“IPCHiP is the first major global clinical collaboration around genomics and precision child health,” he said. Thanks to our international partnership focused on rare diseases, we can forge innovative diagnostic solutions and work towards new treatments that improve health outcomes.”

IPCHiP’s initial flagship project, Gene-STEPS found that rapid genome sequencing was highly effective at diagnosing babies with epilepsy and lead to better, more targeted treatment options in most cases. The research, published in The Lancet Neurology, reported rapid genome sequencing had a high diagnostic rate of 43 per cent for infantile epilepsy, supporting the need for greater access to the cutting-edge technology in clinical care.

MCRI Professor John Christodoulou said a top priority of IPCHiP was exploring approaches that could overcome challenges around how data was currently shared, accessed and used international.

“The team is using the Gene-STEPS findings to establish a data network that will allow shared analysis of clinical and genomic information generated from collaborative projects for any paediatric rare disease,” he said.

“Genomic data obtained in childhood and from reproductive carrier screening will help us in the future to tackle the common health issues such as heart disease and cancer.”

IPCHiP is expanding its work on rapid genomic testing to other genetic conditions that could benefit from a prompt diagnosis. Its next cohort, GEMStone, will focus on newborns with hypotonia, where a baby is born with low muscle tone, which can lead to difficulties in feeding, holding their head up and achieving developmental milestones.

Publication: Katherine B. Howell, Susan M. White, Amy McTague, Alissa M. D’Gama, Gregory Costain, Annapurna Poduri, Ingrid E Scheffer, Vann Chau, Lindsay D. Smith, Sarah EM Stephenson, Monica Wojcik, Andrew Davidson, Neil Sebire, Piotr Sliz, Alan H. Beggs, Lyn S Chitty, Ronald D. Cohn, Christian R. Marshall, Nancy C. Andrews, Kathryn N North, J. Helen Cross, John Christodoulou and Stephen W. Scherer. ‘International Precision Child Health Partnership (IPCHiP): an initiative to accelerate discovery and improve outcomes in rare pediatric disease,’ npj Genomic Medicine. DOI: 10.1038/s41525-025-00474-8

Available for interview:

Dr Katherine Howell, MCRI, Group Leader, Neuroscience

Professor John Christodoulou, MCRI, Theme Director, Genomic Medicine

Professor Stephen Scherer, SickKids, Chief of Research 

 

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