1 - Unidade de Neuropediatria, Área da Mulher, Criança e Adolescente, Hospital D. Estefânia, Centro Hospitalar Lisboa Central, Lisboa
2 - Institute of Child Health, University College London, London
3 - Cambridge Institute for Medical Research, University of Cambridge, Cambridge
- Apresentado sob a forma de Comunicação Oral na Reunião nacional
- 30º Encontro Nacional de Epileptologia
- 9 e 10 de Março de 2018, Coimbra, Portugal
Resumo:
Background and aims: The use of Next Generation Sequencing(NGS), exome and panels, in the previous years has allowed major advances on the identification of causative genes of paediatric epileptic encephalopahies(EE).
Methods: Review of clinical files of children with EE due to new genes identified by NGS since 2012.
Results: We present 10 children (7 boys, 17months-21 years), all presenting with seizures refractory to medical treatment in the newborn period and all evolving to global developmental delay without dysmorphic features or organomegalia. A few distinctive clinical features include global severe hypotonia and scarce spontaneous movements in the child with SLC25A22 mutation and spastic tetraparesis related to KCNQ2, GRIN2A and SCNL2A. The child with MEF2C mutation presents continuous stereotypies and the one with SPTAN1 mutation also shows Rett-like stereotypies but also global chorea and dystonia. One of the 2 children with STXBP1 mutation has autism. All children presented with global lentification of eletrogenesis except ATP1A3 and multifocal paroxystic activity on EEG. SCNL2A mutation was the only associated with neonatal burst –suppression pattern and ATP1A3 with nonconvulsive status epilepticus. The only consistent positive response to treatment occurred with the use of ketogenic diet on the children with ATP1A3 and GRIN2A mutations.
Conclusion: The recognition of new causative genes of paediatric EE allows the recognition of suggestive phenotypes, more individualized treatment directed to the dysfunction of codified proteins and paves the way to eventual future genetic treatment. All genes involved code for proteins relevant for synaptic function.
Palavras Chave: Epileptic Encephalopathies; Next Generation Sequencing; Synaptic dysfunction;