About Epilepsy

Epilepsy is a common and very stigmatizing neurological disease affecting about 0.5 to 1% of the world population. In Tunisia, the prevalence of epilepsy has been estimated at 3.8 per 1000 persons. Epilepsy is more frequent in children, about 70% of the cases occur before the age of 20 with a peak observed during the first year. In this age group, epilepsy is common and present in the majority of cases as a complex epilepsy phenotype. Studies showed that 30% of children presenting with epilepsy before 36 months are medically intractable and 36% of epilepsy starting before 24 months manifest as Epileptic Encephalopathies (EEs). EEs are a group of heterogeneous epileptic syndromes associated with severe cognitive stagnation or regression and behavioral disturbances. Approximately 40% of seizures with onset in the first 3 years of life will progress to developmental EE, and a substantial number of these are associated with variants in known epilepsy genes. The key concept of EE is that cognitive regression improves with improvements in epilepsy and EEG abnormalities, hence the importance of early diagnosis and treatment. Indeed, growing evidence suggests that early, effective intervention for seizures may modify the severity of developmental behavioral, and other outcomes in some EE syndromes. A prospective population-based study identified an EE in 39% of epileptic infants and in Sfax child neurology department, EE was identified in 43% of children with epilepsy. However, the overall incidence of EE was probably underestimated because many disorders in children were not classifiable despite severe neurodevelopmental sequelae.
In clinical terms, EE represent a very heterogeneous group of electro-clinical syndromes with complex phenotypes that require advanced and precise knowledge. ILAE distinguishes several well-known electro-clinical syndromes (e.g West syndrome or Dravet syndrome,…). Determining the etiology of EE is a real challenge. Indeed, the causes are numerous with significant phenotypic overlap; these include non genetic causes as well as genetic causes.
A substantial number of patients with EE do not have phenotypes that fit into specific epilepsy syndromes, and this hampers a clear clinical diagnosis and prevents straightforward genetic testing. Indeed, clinical features are suggestive of the underlying genetic cause in one third of patient1. However, to describe the phenotype of these epileptic syndromes, one needs a significant experience of electro-clinical symptoms of seizures. Access to both EEG and video-EEG monitoring to enables in-depth electrophysiological phenotyping, is mandatory for genetic orientation and delineation of novel genetic entities and genotype-phenotype correlation studies.
EE can be monogenic and identification of the underlying causative gene helps with diagnosis. With the advent of sophisticated molecular diagnostic techniques, rapid growth in gene discovery for epileptic encephalopathies has occurred (30-50%) and broadened gene-specific phenotypes resulting in a revival of interest for the group of patient1. Given the high genetic heterogeneity observed for these diseases, clinical phenotyping is key for the interpretation of the identified genetic variants.

1 Kothur K, Seizure 2018
2 Palmer EE, Mol Genet Genomic Med. 2018