Genomic Investigation of Infantile and Childhood Epileptic Encephalopathies in Kazakhstan: An Urgent Priority

Abstract

Objectives: Infantile and childhood epileptic encephalopathies are a group of severe epilepsies that begin within the first year of life and often portend increased morbidity. Many of them are genetically determined. The medical strategy for their management depends on the genetic cause. There are no facilities for genetic testing of children in Kazakhstan but we have a collection of data with already defined genes responsible for clinical presentations.Methods: We analyzed children with epileptic encephalopathies that began in the first 3 years of life and were accompanied by a delay/arrest of intellectual development, in the absence of structural changes in the brain. Such patients were recommended to undergo genetic testing using epileptic genetic panels in laboratories in different countries.Results: We observed 350 infants with clinical presentation of epileptic encephalopathies. 4.3% of them followed our recommendations and underwent genetic testing privately. In total 12/15 children became eligible for targeted treatment, 3/15 were likely to have non-epileptic stereotypies/movements, 2/15 were unlikely to respond to any therapy and all had a high chance of intellectual disability, behavioral and social communication disorders.Conclusion: The genetic results of 15/350 (4.3% of patients) have demonstrated the potential and enormous impact from gene panel analysis in management of epileptic encephalopathy. Availability of genetic testing within the country will improve management of children with genetic epilepsies and help to create a local database of pathogenic variants.

Whole-Genome Sequencing Among Kazakhstani Children with Early-Onset Epilepsy Revealed New Gene Variants and Phenotypic Variability

“…The following genes have been identified as epilepsy etiology: ARX , CACNA1B , CASK , CHRNA2 , GRIN2D , KCNQ2 , KCNT1 , MT-CO3 , PCDH19 , SCN1A (x2), SLC2A1 , SLC12A5 , and WWOX . In an early study, Jaxybayeva et al [ 6 ] identified a genetic cause in 80% (12/15) of children with early seizures using whole-exome sequencing in Kazakhstan ( CDKL5 (x3), SCN1A (x2), MECP (x2), STXBP1 , UBE3A , PCDH19 , FOLR1 , PNPO ). Summing up the results from the present and the above mentioned studies, which is acceptable due to relatively similar inclusion criteria, the overall detection rate for the genetic etiology of early-onset epilepsy was 74.3% (26/35).…”

“…In the pediatric population, epilepsy is a common neurological disorder affecting approximately 0.5 to 1% of children [ 5 ]. According to Jaxybayeva et al [ 6 ] in Kazakhstan, as of October 2020, epilepsy was diagnosed in 15,769 children (aged 0 to 18). Among 450 (32% of total hospitalizations) patients with epilepsy hospitalized in the Department of Pediatric Neurology of the National Scientific Center for Maternal and Child Health of “University Medical Center”; Corporate Found (CF) between 2013 and 2014, 170 of them were diagnosed with epileptic encephalopathy [ 7 ].…”