Predictive factors of genetic diagnosis and real‐life impact of next‐generation sequencing for children with epilepsy

Abstract

ObjectiveIdentify the predictive variables of genetic pathogenic results and the impact of test results on epilepsy diagnosis and management.MethodsAnalytical observational design evaluated 130 patients with epilepsy that had performed genetic testing over January 2017 to July 2022.ResultsThere was a gradual increase in the number of exams performed over the years. The frequency of pathogenic results was 34% (n = 44/130), 8 altered genes with 54% (n = 24/44) of the results. The tests were more positive in patients with developmental delay and/or regression (p = .01). None of the other factors analyzed were associated with higher diagnostic yield. The age at onset of epilepsy brought diagnostic yield to the test (p = .041). Patients with negative genetic test had a reduction in the number of electroencephalograms performed before and after the test (respectively, 3.80 ± 6.37 and .84 ± 1.67; p < .001).SignificanceFacing a large proportion of patients with unexplained epilepsy have a genetic cause a genetic test has the potential to reduce the use of unnecessary diagnostic tests, improve patient outcomes by identifying targeted treatments, and provide families with genetic counseling and risk assessment. But an early genetic testing can be crucial to reach these goals. Even in cases where the genetic test is negative, the study suggests that it still has important implications for patient care and management.

Accessibility, availability and common practices regarding genetic testing for epilepsy across Europe: A survey of the European Reference Network EpiCARE

“… 15 However, genetic testing has emerged as an indispensable tool in epilepsy care. 4 , 5 , 6 We have thus attempted to use some common representation methods in order to provide an insight on the topic, as illustrated in the maps created for the needs of this project. In fact, according to our survey, the Western countries seem to be better provided in terms of genetic testing, as they were better provided for the indication factors of epilepsy care measured for the ESBACE study.…”

“…4 The advances in epilepsy genetics and next-generation sequencing (NGS) over the past two decades have led to the discovery of hundreds of new genes and pathogenic variants and to the emerging of targeted therapies. 5,6 This new genomic era in epilepsy and other neurological disorders comes along with an increased interest in an earlier identification of genetic etiologies and several challenges to the clinicians. 7 For example, the clinicians need to stay updated regarding the continuously expanding phenotypical spectrum of specific monogenic epilepsies on the one hand and the overlapping of similar phenotypes related to different genes on the other.…”

“… 4 The advances in epilepsy genetics and next‐generation sequencing (NGS) over the past two decades have led to the discovery of hundreds of new genes and pathogenic variants and to the emerging of targeted therapies. 5 , 6 …”

Evaluating Clinical Presentation and Long-Term Outcomes in Individuals with Genetic and Non-Genetic Epilepsy Treated with Epilepsy Surgery: A Single-Center Study

“…Indeed, developmental delay of different severity is a feature of numerous genetic disorders associated with epilepsy. The yield of genetic testing in individuals with epilepsy increases if concurrent developmental delay is present 33,34 , making this combination of clinical features an important triaging factor for genetic testing.…”

“…We matched individuals with non-genetic epilepsy separately to individuals with mTORopathies and other genetic epilepsy etiologies using 1:1 nearest-neighbor matching on propensity scores. Propensity scores were derived by running a generalized linear regression model where the dependent variable was the genetic status, and predictors included clinical variables known to be associated with postsurgical outcomes 33,34 : sex, age at seizure onset and surgery, presence of MRI lesion, presence of developmental delay, preoperative seizure frequency, EEG findings at presurgical evaluation, and side and extent of intervention. Individuals with mTORopathies were matched with individuals with non-genetic epilepsies first.…”