Title : Genetic background of DEE amongst Egyptian children

DEE is the most severe group of epilepsy. This group of disorders is characterized by seizures associated with slowing or regression in milestones of development. The condition starts in infancy or childhood and includes several well defined epileptic syndromes.

These patients suffer from a range of comorbidities including mental disabilities, psychiatric, behavior problems such as ASD, sleep problems, musculoskeletal disorders and a higher rate of mortality.

The condition persists throughout the patients' lives with more symptoms evolving with age. Therefore, lifelong treatment and care is essential. This adds a high psychosocial burden on the families and community.

With the use of next generation sequencing technologies, more than 50% of the patients with DEE the aetiology and genetic causes of the disorders were identified. Over 900 heve been confirmed as monogenic cause of DEE. These genes control and contribute to the cellular function, pathophysiology such as ion channels and transporters, synaptic processes, cell signaling and metabolism, as well as epigenetic regulations.

The identification of the specific underlying aetiology allow the development of precision medicines to improve the long term outcome of these patients and their quality of life.

Introduction: DEE is a complex concept consisting of 2 facets; a developmental encephalopathy which leads to intellectual disability coupled with an epileptic encephalopathy. The epileptic activity itself contributes to further cognitive and behavior deterioration on top of that caused by the underlying pathology alone. The hallmark of this complex is slowing and regression in their cognitive development.

Objectives: The diagnosis of DEE and identification of the genetic background of this heterogeneous group of disorders will allow to develop or modify the therapeutic strategies, that will improve the epileptiform activity and subsequently allow the patients make developmental gains.

Specific DEE syndromes, early diagnosis and detection, appropriate management may facilitate a good outcome and allow children to have normal intellect (for example in the case of epileptic encephalopathy of epilepsy with myoclonic-atonic seizures).

Methodology: Twenty DNA samples will be collected from 20 Egyptian children suffering from DEE, confirmed by clinical, brain MRI, EEG, and suffered from decline in neurocognitive developmental abilities. There neurodevelopmental symptoms were regressive in nature. DNA will be subjected to WES/WGS in order to identify genetic variants within this cohort.  

Further analysis of the results will aim to investigate the role of these genetic variants on cell metabolism, signaling pathways, synaptopathies and channelopathies involved in epileptogenic activity and normal brain development. Subsequently, this will allow therapeutic modifications and precision medicine aiming to improve the clinical outcome of these patients as well as their families.

Evaluation: This cohort will be followed up in order to evaluate the significance of the therapeutic modification clinically, developmentally and psychologically. Also their families will be better counselled for future family planning, prenatal genetic diagnosis and prevention.

The samples will be collected from Egyptian children suffering from DEE to allow investigating the genetic implications of this disorder within a specific ethnic population, which has not been targeted before.   

To be updated shortly..