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14-09-2023 | Epilepsy | Editor's Choice | News

Rapid genome sequencing shows high diagnostic yield in new-onset epilepsy

Author: Radhika Dua


medwireNews: Rapid genome sequencing in infants with new-onset epilepsy is feasible in the clinical setting, show findings from the international multicenter Gene-STEPS study.

Rapid genome sequencing resulted in genetic diagnoses being made in 43% of 100 infants with new-onset epilepsy or complex febrile seizures before the age of 12 months, Amy McTague (UCL Great Ormond Street Institute of Child Health, London, UK) and colleagues report in The Lancet Neurology

In a comment accompanying the study, Katrine Johannesen and Rikke Møller, both from The Danish Epilepsy Centre in Dianalund, say that it highlights “the utility of genome sequencing as a first-line diagnostic tool for epilepsy,” and suggests that rapid genome sequencing could facilitate prompt initiation of targeted treatments and uptake of clinical testing, family counseling, and patient prognosis.

The infants included in the study were enrolled from four pediatric centers in Australia, Canada, the UK, and the USA as part of the International Precision Child Health Partnership. The researchers note that most of the participants were recruited from non-intensive care inpatient or outpatient settings (43% and 40%, respectively) rather than intensive care (17%). The majority (59%) of infants were boys and the median age of seizure onset was 128 days.

Blood samples were collected from the infants and available biological parents, and depending on parental availability, rapid genome sequencing was performed using trio (91% of families), duo (8%), or singleton (1%) sequencing.

McTague et al note that the 43% diagnostic yield is comparable to previously reported yields with nonrapid genome sequencing and higher than that for chromosomal sequencing, gene panels, and exome sequencing.

And they stress that the median time from study enrolment to receiving a rapid genome sequencing result was just 21 days, which “represents a major improvement over current standard of care.”

The researchers found that a genetic diagnosis was significantly more common in infants with neonatal seizure onset versus infantile seizure onset, and in those with self-limited epilepsies.

A genetic diagnosis was also more common among patients who were assessed in the intensive care setting, at 71%, but the investigators highlight that the success of the technique extended beyond this, with diagnoses made in 44% of nonintensive care inpatients and 28% of outpatients. This expansion means more infants can benefit from early genetic diagnoses, improving their chances of receiving timely and suitable care, they explain.

This technique identified a wide range of genetic heterogeneity, implicating 34 unique genes or genomic regions, the researchers note. Moreover, the study authors highlight the immediate impact a genetic diagnosis had on clinical management. Antiseizure medication was initiated in 56% of diagnosed infants, including potential precision therapies in 49%, while 65% of infants underwent additional evaluation, 86% received prognosis information, and all cases received recurrence risk counseling.

The researchers conclude: “We demonstrate feasibility of rapid genome sequencing in infants with new-onset epilepsy across multiple tertiary paediatric systems, with high diagnostic yield and clinical effect.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group

Lancet Neurol 2023; 9: 812–825
Lancet Neurol 2023; 9: 773–774


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