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. 2020 Nov;61(11):2486-2499.
doi: 10.1111/epi.16701. Epub 2020 Sep 23.

Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study

Tommy Stödberg  1   2 , Torbjörn Tomson  3 , Michela Barbaro  4   5 , Henrik Stranneheim  4   5   6 , Britt-Marie Anderlid  4   7 , Sofia Carlsson  8 , Per Åmark  1 , Anna Wedell  4   5   6
Affiliations

Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study

Tommy Stödberg et al. Epilepsia. 2020 Nov.

Abstract

Objective: Population-based data on epilepsy syndromes and etiologies in early onset epilepsy are scarce. The use of next-generation sequencing (NGS) has hitherto not been reported in this context. The aim of this study is to describe children with epilepsy onset before 2 years of age, and to explore to what degree whole exome and whole genome sequencing (WES/WGS) can help reveal a molecular genetic diagnosis.

Methods: Children presenting with a first unprovoked epileptic seizure before age 2 years and registered in the Stockholm Incidence Registry of Epilepsy (SIRE) between September 1, 2001 and December 31, 2006, were retrieved and their medical records up to age 7 years reviewed. Children who met the epilepsy criteria were included in the study cohort. WES/WGS was offered in cases of suspected genetic etiology regardless of whether a structural or metabolic diagnosis had been established.

Results: One hundred sixteen children were included, of which 88 had seizure onset during the first year of life and 28 during the second, corresponding to incidences of 139 and 42/100 000 person-years, respectively. An epilepsy syndrome could be diagnosed in 54% of cases, corresponding to a birth prevalence of 1/1100. Structural etiology was revealed in 34% of cases, a genetic cause in 20%, and altogether etiology was known in 65% of children. The highest diagnostic yield was seen in magnetic resonance imaging (MRI) with 65% revealing an etiology. WES/WGS was performed in 26/116 cases (22%), with a diagnostic yield of 58%.

Significance: Epilepsy syndromes can be diagnosed and etiologies revealed in a majority of early onset cases. NGS can identify a molecular diagnosis in a substantial number of children, and should be included in the work-up, especially in cases of epileptic encephalopathy, cerebral malformation, or metabolic disease without molecular diagnosis. A genetic diagnosis is essential to genetic counselling, prenatal diagnostics, and precision therapy.

Keywords: epilepsy syndrome; etiology; incidence; infantile epilepsy; next-generation sequencing.

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Conflict of interest statement

T Tomson received speaker's honoraria to his institution from Eisai, Sanofi, Sun Pharma, UCB, and Sandoz, and received research support from GSK, UCB, Eisai, and Bial. S Carlsson received grants from Novo Nordisk Foundation. The remaining authors have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Classification of 163 cases retrieved from the Stockholm Incidence Registry of Epilepsy (SIRE), after reevaluation by two authors (TS and PÅ)
FIGURE 2
FIGURE 2
Age distribution of the first unprovoked epileptic seizure (onset seizure) in 116 cases of epilepsy
See this image and copyright information in PMC

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