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An international study has sequenced the genomes of 100 infants with unexplained seizures, along with their parents to better understand the potential strengths of early, broad genome sequencing for infantile epilepsy.

The researchers used rapid genome sequencing to investigate the impact of an expedited genetic diagnosis on care for the first time. Across all children enrolled in the study, 43 percent received a diagnosis within weeks, and that diagnosis impacted prognosis in nearly 90 percent of those cases, guiding treatment options for over half.

Annapurna Poduri, study co-lead and Director of the Neurogenetics and Epilepsy Genetics Programs at Boston Children’s Hospital, said: “The status quo has been to treat seizures like a symptom and try to find medications that alleviate them. But medications aren’t getting at the underlying causes of epilepsy.”

The study appeared in The Lancet Neurology last week. The lead author is Alissa M. D’Gama, PhD, of Boston Children’s Hospital.

Epilepsy in infants ranges in severity. While genetic testing to help determine the cause of epilepsy is possible, comprehensive testing does not always happen routinely and it can take a long time, leaving families waiting for answers.

Named Gene-STEPS (Shortening Time to 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 in Melbourne Australia, The Hospital for Sick Children (SickKids) and UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital) that leverages each institution’s expertise and genomic infrastructure to accelerate discovery and the development of therapies for children.

Currently, there are more than 800 different genetic causes of infantile epilepsy and many have similar symptoms during infancy. Unlike more targeted genetic testing that is often used to confirm a suspected diagnosis, rapid genome sequencing looks for any changes in a person’s DNA that may explain a medical condition, analyzing the entire genome.

In this study, both biological parents and the infant 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 may impact their lives and any future family planning.

Amy McTague, study co-lead and clinician scientist at the UCL Great Ormond Street Institute of Child Health, 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 infants with new-onset epilepsy.

For the participants for whom initial analysis did not provide a genetic explanation for their seizures, the research team noted that a “negative” result from this genetic test was also an important piece of information for families and clinicians, providing an informed path forward for the child’s care.

The international research team is continuing to follow-up with clinicians and study participants to understand how rGS has influenced the child’s development, but the work doesn’t stop there. A greater understanding of the genetic variants involved in epilepsy may help identify eligibility for clinical trials and inform the development of tailored interventions.

Poduri said, “We demonstrated that if providing an underlying diagnosis to families and providers—quickly—was made a priority, we could better inform future treatment, evaluation, prognosis, and counseling for families of kids with infantile epilepsy.”

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