Maurizio Taglialatela, M.D., Ph.D. - "KCNQ2 encephalopathy: from pathogenetic mechanisms to personalized treatments"
Feb 14, 2017
from 12:00 PM to 01:30 PM
|Where||tigem Auditorium "Vesuvius"|
|Contact Name||Andrea Ballabio|
|Add event to calendar||
Mutations in KCNQ2 encoding for voltage-gated potassium channel subunits are responsible for neonatal-onset epileptic diseases with a heterogeneous phenotypic presentation. On the benign end of the spectrum is familial neonatal seizures (BFNS), an autosomal-dominant epilepsy characterized by recurrent seizures beginning in the first days of life and remitting after a few weeks or months, with mostly normal interictal EEG, neuroimaging, and psychomotor development. By contrast, de novo missense KCNQ2 mutations can lead to a severe epileptic encephalopathy (KCNQ2-EE), in which neonates develop pharmacoresistant seizures with distinct EEG and neuroradiological features, and various degrees of developmental delay. De novo missense Kv7.2 mutations are responsible for 10-20% of neonatal-onset epileptic encephalopathies. In this lecture I will review the multiplicity of pathogenetic mechanisms responsible for disease occurrence in KCNQ2-EE caused by distinct gene variants. Given that, similarly to other genetically-determined EEs, both loss and gain-of-function molecular mechanisms have been identified in Kv7.2-EE, efforts to understand the molecular pathogenesis in Kv7.2-EE are crucial to deduce genotype-phenotype correlations which may improve diagnostic and prognostic efforts, and guide therapeutic approaches. Finally, I will review the advantages and limitations of the recent therapeutic attempts made with the KCNQ opener retigabine in children with KCNQ2-EE, and the current status of drug development in this area.