Clinical predictors of positive genetic investigation of the developmental and epileptic encephalopathies

Objectives: Genetic tests expanded the landscape of developmental and epileptic encephalopathies (DEEs), making essential the rational genetic investigation (Berg AT, 2017; Palmer EE, 2021). The present study evaluated the clinical predictors of positive genetic investigation in DEE. Methods: 66 patients with DEE followed in the Clinical Hospital of Campinas University (UNICAMP) were submitted to Sanger sequencing of SCN1A gene, chromosomal microarray analysis, and whole exome sequencing. The association of clinical, electroencephalogram (EEG) and neuroimaging data with a positive genetic test was investigated using univariate and multivariate analysis. Results: The genetic etiology was defined in 34 (51.1%) patients with DEE. Positive genetic evaluation was associated with female sex (OR 3.0, CI 95% 1.06–8.53, p = 0.03), first febrile seizure (OR 19.2, CI 95% 2.22–157.97, p < 0.01) and focal seizures (OR 3.6, CI 95% 1.2–10.04, p = 0.01). Negative genetic evaluation was associated with generalized discharges on the EEG (OR 0.4, CI 95% 0.13–0.98, p = 0.04), diagnosis of epilepsy with myoclonic-atonic seizures (MAE) (OR 0.1, CI 95% 0.01–0.48, p < 0.01) and Lennox-Gastaut syndrome (LGS) (OR 0.2, CI 95% 0.04–0.64, p < 0.01). The diagnosis of MAE (p = 0.02) and LGS (p = 0.03) were independently associated with a negative genetic test. Conclusion: In this cohort of DEE, female sex, first febrile seizure and focal seizures increased the chances of a positive genetic test; whereas generalized discharges on the EEG, and a diagnosis of MAE or LGS decreased the chances.
Keywords: Developmental and epileptic encephalopathies; Epilepsy; Genetic.