Diagnostic evaluation of patients with epileptic spasms in the era of next-generation sequencing.

Autor: Mir A; Department of Pediatric Neurology, King Fahad Specialist Hospital, Dammam, Saudi Arabia., AlQahtani M; Department of Pediatric Neurology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.; Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada., Amer F; Department of Pediatric Neurology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.; Department of Pediatric Neurology and Metabolic, Cairo University Children Hospital, Cairo, Egypt., AlBaradie R; Department of Pediatric Neurology, King Fahad Specialist Hospital, Dammam, Saudi Arabia., AlOtaibi W; Department of Pediatric Neurology, King Fahad Specialist Hospital, Dammam, Saudi Arabia., AlGhamdi F; Department of Pediatric Neurology, King Fahad Specialist Hospital, Dammam, Saudi Arabia., Khallaf H; Genetic and Metabolic Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia., Bashir S; Neuroscience Centre, King Fahad Specialist Hospital, Dammam, Saudi Arabia., Costain G; Program in Genetics and Genome Biology, Division of Clinical and Metabolic Genetics, SickKids Research Institute and Hospital for Sick Children, Toronto, Ontario, Canada., Aljouda L; Program in Genetics and Genome Biology, Division of Clinical and Metabolic Genetics, SickKids Research Institute and Hospital for Sick Children, Toronto, Ontario, Canada., Housawi Y; Genetic and Metabolic Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
Jazyk: angličtina
Zdroj: Epileptic disorders : international epilepsy journal with videotape [Epileptic Disord] 2024 Oct; Vol. 26 (5), pp. 651-661. Date of Electronic Publication: 2024 Jul 01.
DOI: 10.1002/epd2.20259
Abstrakt: Objective: Epileptic spasms (ES) can be caused by a variety of etiologies. However, in almost half of cases, the etiology is unidentified. With the advent of next-generation sequencing (NGS), the recognition of genetic etiologies has increased.
Methods: We retrospectively reviewed the medical records of patients with ES who were evaluated in the comprehensive epilepsy program at King Fahad Specialist Hospital Dammam between 2009 and 2022.
Results: Our data show that in 57.7% of patients with ES, the etiology was unidentified after a standard clinical evaluation and neuroimaging. Of these patients, n = 25 (35.2%) received a genetic diagnosis after some form of genetic testing, and 3.1% of patients from specialized metabolic work indicated the need for genetic testing to confirm the diagnosis. Karyotyping led to a diagnosis in 3.6% of patients, and chromosomal microarray led to a diagnosis in 7.1%. An NGS epilepsy gene panel (EP) was done for 45 patients, leading to a diagnosis in 24.4% (n = 11). Exome sequencing was done for 27 patients, including n = 14 with non-diagnostic panel testing; it led to a diagnosis in 37.3% (n = 10). Exome sequencing led to a diagnosis in 61.5% of patients without a previous panel test and in only two patients who had previously had a negative panel testing.
Significance: In this article, we present the diagnostic evaluations of ES for a cohort of 123 patients and discuss the yield and priority of NGS for evaluating ES. Our findings suggest that exome sequencing has a higher diagnostic yield for determining the etiology of ES in patients for whom the etiology is still unclear after an appropriate clinical assessment and a brain MRI.
(© 2024 International League Against Epilepsy.)
Databáze: MEDLINE
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