Dados do Trabalho

Título

GENETIC EPILEPTIC AND DEVELOPMENTAL ENCEPHALOPATHIES AND ASSOCIATED CLINICAL FACTORS

Introdução

Epileptic and Developmental Encephalopathies (DEE) are defined by frequent epileptiform activity and seizures, behavioral and cognitive symptoms. Recently, new DEE-associated genes were identified. SCN1A is the most recognized gene, related to varied phenotypes, including Dravet Syndrome (DS). Beyond high positivity rate of DS, data of clinical factors associated with positive genetic test is scarce.

Objetivo

To investigate the clinical factors associated with positive genetic test of DEE beyond the influence of DS.

Método

The study included 107 patients diagnosed with DEE. All patients were submitted to Sanger sequencing of SCN1A, Chromosomal Microarray Analysis (CMA) and/or Whole Exome Sequencing (WES). The association of clinical variables with positive genetic test was investigated with univariate analysis.

Resultados

Genetic diagnosis was identified in 56 (52%) patients with DEE. Female sex (OR3.6(1.2–5.9), p=0.02), first febrile seizure (OR5.4(2.1–14.1), p<0.01), seizures precipitated by temperature (OR3.4(1.5–8.0), p< 0.01), focal seizures (OR2.3(1.0–5.3), p=0.04), cognitive regression (OR2.3(1–5.1), p=0.04), autism spectrum disorder (OR2.4(1.1–5.6), p=0.03), onset of seizures at infancy (OR3.2(1.4–7.5), p<0.01) were positively associated with genetic diagnosis. Distinctly, atonic seizures (OR0.2(0.1–0.6), p<0.01), EEG with generalized discharges (OR0.3(0.1–0.7), p<0.01) or generalized paroxysmal fast activity (OR0.2(0.04–0.9), p=0.04), onset of seizures at pre-school age (OR0.2(0.1–0.6), p<0.01) were negatively associated with genetic test. DS-patients represented 20% of the sample (77% with SCN1A variants). When DS-patients were excluded, genetic diagnosis was found in 43.5%. Variables that remained associated with positive genetic test were first febrile seizure (OR5.2(1.5–18.1), p=0.01), cognitive regression (OR3.1(1.3–7.9), p=0.01), atonic seizures (OR0.3(0.1–0.8), p=0.01), generalized discharges in EEG (OR0.3(0.1–0.7), p<0.01), onset of seizures during pre-school age (OR0.2(0.1–0.7), p<0.01). Besides, hypotonia (OR3.2(1.3–7.8), p=0.01) was also positively associated.

Conclusões

Clinical characteristics associated with positive genetic investigation of DEE might change when DS-patients are excluded. First febrile seizure and cognitive regression remained positively associated with a genetic cause for DEE, while atonic seizures, generalized discharges and onset of seizures during pre-school age remained negatively associated.