Recent advances in epilepsy genomics and genetic testing

Abstract

Developmental and epileptic encephalopathies (DEEs) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis. DEE is genetically and phenotypically heterogeneous, and there is a plethora of genetic testing options to investigate the rapidly growing list of epilepsy genes. However, more than 50% of patients with DEE remain without a genetic diagnosis despite state-of-the-art genetic testing. In this review, we discuss the major advances in epilepsy genomics that have surfaced in recent years. The goal of this review is to reach a larger audience and build a better understanding of pathogenesis and genetic testing options in DEE.

Description of neurodevelopmental phenotypes associated with 10 genetic neurodevelopmental disorders: A scoping review

“…The oldest reported individuals in the epilepsy associated genes were relatively younger than in other genes (Table 2). This may be due children presenting with seizures and receiving genetic testing at an earlier age 21 . In addition, early mortality associated with epilepsy may result in less reporting of cognitive and functional outcomes into adulthood in genes associated with epileptic encephalopathies 22 …”

Investigating rare and ultrarare epilepsy syndromes with Drosophila models

“…Forward genetic screens in Drosophila have identified factors affecting general functions such as sleep 23 as well as many that associate with ID and autism spectrum disorder 24 . With respect to epilepsy, geneticists and clinicians have identified causative variants in more than 100 genes, the majority of which have conserved orthologs in Drosophila , enabling fast and inexpensive modeling of human patients’ conditions 25 , 26 . Even the intricate role of glial cell contribution to hereditary epilepsies has been investigated through interactions that have been conserved on the level of both molecular and cellular interactions 27 , 28 .…”

An advance about the genetic causes of epilepsy

“…Among all K+ channel families, the Kv family (voltagegated K channel) in the K+ channel family is considered the most related family with human epilepsy [3]. There are approximately 40 types of genes encoding for the Kv family, and 12 of them are strongly implicated in epilepsy [4,5]. The potassium voltage-gated channel subfamily A member 1 (KCNA1) gene codes for the Kv1.1 subunit on the axonal membrane and presynaptic nerve terminals contribute to membrane repolarization and formation of action potentials.…”