Dados do Trabalho

Título

GENETIC PROFILE OF PATIENTS WITH DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY AT A REFERENCE CENTER IN NORTHEAST BRAZIL

Introdução

The developmental and epileptic encephalopathy (DEE) diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. Many DEEs have a genetic basis that, by themselves, can alter the neurodevelopmental delay. By August 2022, there were 105 genes associated with DEE according to OMIM.

Objetivo

This study aims to analyze and characterize the profile of patients with DEE followed up in a center in Northeast Brazil.

Métodos

Quantitative, descriptive, retrospective, observational study carried out at a neurogenetic reference center in Northeast Brazil.Patients with a confirmed genetic diagnosis.

Resultados

The sample has 16 patients, no prevalence between sexes, ages 2 to 13 years. Variants were found in 13 genes; ALG13; CDKL5; CHD2; DNM1; GNAO1; KCNQ3; KCNT1; PCDH19; PNKP; SCN1A; SCN1A; SCN1A; SLC12A5; STXBP1; WWOX Only 5 of the variants were previously described as pathogenic. One of the patients had DEE 2 (CDKL5), and had a global cortical volumetric reduction, in addition to l-dopa-responsive movement disorder. The patient with the earlier onset, neonatal, has a variation in the KCNQ3. 3 of the patients analyzed, all boys, had alterations in the SCN1A, among them 2 brothers, non-consanguineous parents, with the same variation, in heterozygosity, both evolving with regression of the neurodevelopmental. The third child with an alteration in the SCN1A had onset of symptoms at 4 months of age and regression at 2 years of age, being the only patient using cannabidiol. Two patients had variants in the KCNT1. One patient had two heterozygous variants in the SLC12A5, never described in the medical literature, started seizures at 2 months, progressing to death at 8 months. The patient with GNAO1 variation had axial hypotonia, in addition to appendicular dystonia. The patient with a change in the PCDH19 has probable somatic mosaicism and evolved with language regression after the onset of seizures.

Conclusões

This work demonstrates the variability of signs and symptoms found in DEEs. It is still necessary to carry out more genetic screening for patients with early onset epilepsy and/or difficult to control, (9 out of 16 undescribed variations). In addition, some DEEs present specific therapies, such as SCN1A, which should avoid channel blockers. Therefore, the earlier the diagnosis, the sooner we can initiate adequate treatment to reduce the morbidity and mortality of such patients.

Palavras chave

developmental and epileptic encephalopathy, genetic diagnosis, neurodevelopmental delay

Referências (se houver)

Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores

Nenhum dos autores do trabalho do presente trabalho possui conflito de interesse

Área

Neurogenética