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Rapid Whole-Genome Sequencing-Informed Precision Medicine for Critically Ill Children by Stephen F. Kingsmore

At the Festival of Genomics and Biodata 2021, we were joined by Stephen F. Kingsmore (President and CEO, Rady Children’s Hospital) where he discussed rapid newborn sequencing efforts at Rady and how this provides precision medicine opportunities for critically ill children.

End of the odyssey

Kingsmore began his talk by laying out the goals of Rady Children’s Institute. He said that the most important thing is to end the patient diagnostic odyssey. For many rare diseases, the time to diagnosis is very long. Patients often have to attend multiple appointments with multiple physicians before they receive a diagnosis. Kingsmore noted that every child who has a genetic disorder should receive a diagnosis at/before delivery or at onset of symptoms. He emphasised that the Institute wants to end this so “it becomes a part of history.” The second thing they want to do for children worldwide is to end the therapeutic odyssey. For many genetic disorders, there isn’t much evidence for the treatments the children will receive. He hopes that every family should receive full support of the healthcare system and immediate implementation of effective treatment or the opportunity to participant in experimental treatment.

The path to success

The number of genetic diseases for which we know the molecular basis is growing rapidly. This extreme genetic heterogeneity underpins common patient presentations, including seizures and intellectual disability. This means when an infant or child presents with symptoms, physicians have to consider a staggering number of possible genetic diseases. Most importantly, many of the genetic causes have quite different treatments.

The cost and time of whole-genome sequencing is continually declining. This has made it possible to sequence infants and children within intensive care units (ICUs). Kingsmore discussed work at the Institute which they have been focussing on for a decade which aims to reduce the time to result of whole-genome sequencing. The first genome sequence took 13 years to complete and now later this year the team at Rady will release a paper showing that they have reduced this time to 13 hours.

In the real world

The 13-hour system is only an experimental prototype that is at research stages. In the real world, Kingsmore discussed that stable children get rapid whole-genome sequencing with a median time of 52 hours. Whereas, those unstable with rapidly progressive conditions get ultrarapid whole-genome sequencing which takes about 32 hours to get a result.  

Kingsmore drew upon a recent randomised controlled trial of the analytic and diagnostic performance of rapid genome and exome sequencing in ill infants – NSIGHT2. In this study, 213 infants in ICU were enrolled into the study. All had a critical illness with an unknown aetiology. Genomic sequencing was conducted within 96 hours of admission. In addition, in the interim patients received the best treatment available. Between 21-46% received a diagnostic result in 2 days. Physicians also regarded this information as useful for acute management.

Kingsmore noted other countries that are also implementing rapid whole-genome sequencing, including in England and Wales and also Australia. Additionally, other implementation projects are exploring whether these systems will work in the real-world, including project baby bear. This project resulted in improved health outcomes for 178 critically-ill babies and medical cost saving of $2.5 million.

Registration for on-demand access to watch this talk and all our other talks from the Festival will end on February 12th. Register now.

More on these topics

Infant / Precision Medicine / WGS