Genetic Investigations in Children With Developmental and Epileptic Encephalopathies in Ho Chi Minh City, Vietnam

Early childhood is one of the periods of life in which the risk to develop epilepsy is highest. Besides, genetic causes are much more common in the young. Recently, an ever-increasing amount of genes has been found to be involved in numerous early-onset epilepsies. Thanks to next-generation sequencing (NGS), a diagnosis can now be reached in close to 50% of children with epilepsy and developmental delay. This, in turn, has led to the successful application of the concept of individualized treatment in a growing number of children with epilepsy. Genetic investigations have thus been progressively included in the routine work-up of children with early-onset epilepsies throughout the world, mostly in high-income countries up to now. As a result of a scientific collaboration between pediatric neurology divisions at University Hospitals Geneva (HUG), Switzerland, and Children's Hospital 2 in Ho Chi Minh City (HCMC), Viet Nam, genetic testing of children with early-onset epilepsies followed at the pediatric neurology division, Children's Hospital 2 started at the genetics laboratory of the Vietnam National University in 2017.Aims: Our project aims at establishing the proportion of patients in whom a causal genetic finding can be identified, in a prospective cohort of children with Developmental and Epileptic Encephalopathies (DEE) followed at Children's Hospital 2 (ND2). We also aim at identifying the percentage of these children in whom this approach would change current management.Methods: A series of children diagnosed with DEE and followed at ND2 Hospital, enrolled consecutively. Exome sequencing was applied to all, with biostatistical analyses of a panel of 671 genes involved in epilepsies and developmental disorders performed in parallel at Ho Chi Minh City Vietnam National University and Geneva Genetic Medicine Division. Sanger sequencing confirmation of potentially causal variants in patients, and in parents for familial segregation. Comparison of Vietnamese and Swiss genetic findings, and multidisciplinary discussions in formal Genome Boards. Additional genetic investigations, if deemed necessary in Genome Board sessions. Clinical management adapted to genetic findings wherever applicable, and follow-up according to standard practice. One-hundred-and-fifty patients are expected to participate during the 3-year study period.

Inclusion Criteria:Drug-resistant epilepsy, either from onset, or at follow-up, according to ILAE 2010 criteriaSevere developmental delay or regression, according to paediatric neurologist evaluation (or developmental quotient <50, if formally assessed)Age of onset of principal symptoms (Seizures, Developmental delay): 0-36 monthsAgreement to take part in the study and signed consent formExclusion Criteria:Patients with identified structural, infectious or inflammatory causes (such as perinatal hypoxic-ischemic encephalopathy, Cerebrovascular disorders, Sequelae of trauma or encephalitis, neurocutaneous disorders, etc…) will not be asked to take part to the study.