Abstracts

Rationale: Epileptic encephalopathy (EE) is an electroclinical syndrome and represents a challenge to research and treatment. New technologies in the field of genetics, especially molecular genetics, enable the diagnosis of previously undiagnosed patients. Molecular genetics research since includes a research directed by variants of the technique of polymerase chain reaction (PCR) to the individual sequencing of a gene. When there is a need to investigate conditions that may be caused by alterations in one of many different genes, traditional sequencing techniques (Sanger) are very laborious and costly. The next-generation sequencing of the complete genome or exoma provides a large amount of information about the sequence of DNA at a much lower cost than sequencing using the Sanger technique. It is believed that its use in the investigation of EE clarify enable diagnosis of a significant number of cases.Methods: We evaluated 12 cases of children with epileptic encephalopathy submitted to molecular genetic testing (the genetic sequence of a particular gene, sequencing a panel of genes, known as known etiology of epilepsies and exoma by sequencing). Results: All patients had had seizures in the first two years of life, the mean age of onset of epilepsy was 5,3 months.The seizures were of various types, even in the same patient (Table). An extensive investigation including inherited errors metabolism and neuroimaging tests were negative. Of the 12 cases evaluated to date, seven have had a conclusive diagnosis: two cases of mutation in the SCN1A gene (1 per exome through and 1 resulting the research of specific gene), one case with PCDH19 mutation (panel of genes), one case of mutation in CDKL5 (search specific gene),two cases with mutation of KCNQ2 (exome) and 1 case with gene mutation SCN8A (exome). Of the remaining five cases (inconclusive), two parents are being evaluated for completion of the results, and one patient with a mutation of the CHD 2 (exome) and one with the SRGAP2 (exome) mutation. The other three inconclusives cases, two patients underwent only the panel of genes and one underwent the exome sequencing.Conclusions: Genetic evaluation with modern techniques plays an important role in determining the etiology of epileptic encephalopathies, such as in clinical management, prognosis, genetic counseling or avoiding unnecessary tests. These techniques seem promising regarding the investigation of epileptic encephalopathies without certain etiologies. When the suspicion is not clear enough to indicate the detection of a specific gene, although the gene panel enables the search of a large number of genes, we know that many other genes may be involved and the result of negative panel does not exclude the possibility that the etiology has a genetic cause. The identification of new genes responsible for clinical cases of EE is increasing, and in the near future many new genes will be defined. Such knowledge and experience must be disseminated and shared among centers specializing in the treatment and research of epilepsies.