Genes of Early-Onset Epileptic Encephalopathies: From Genotype to Phenotype

A review the genes more frequently associated with early-onset epileptic encephalopathies:

Early-onset epileptic encephalopathies are severe disorders in which cognitive, sensory, and motor development is impaired by recurrent clinical seizures or prominent interictal epileptiform discharges during the neonatal or early infantile periods. They include Ohtahara syndrome, early myoclonic epileptic encephalopathy, West syndrome, Dravet syndrome, and other diseases, e.g., X-linked myoclonic seizures, spasticity and intellectual disability syndrome, idiopathic infantile epileptic-dyskinetic encephalopathy, epilepsy and mental retardation limited to females, and severe infantile multifocal epilepsy. We summarize recent updates on the genes and related clinical syndromes involved in the pathogenesis of early-onset epileptic encephalopathies: Aristaless-related homeobox (ARX), cyclin-dependent kinase-like 5 (CDKL5), syntaxin-binding protein 1 (STXBP1), solute carrier family 25 member 22 (SLC25A22), nonerythrocytic α-spectrin-1 (SPTAN1), phospholipase Cβ1 (PLCβ1), membrane-associated guanylate kinase inverted-2 (MAGI2), polynucleotide kinase 3′-phosphatase (PNKP), sodium channel neuronal type 1α subunit (SCN1A), protocadherin 19 (PCDH19), and pyridoxamine 5-prime-phosphate oxidase (PNPO).

Summary

Genetic knowledge about early epileptic encephalopathies has revolutionized the diagnostic approach to these disorders, and an increasing number of gene mutations have been related to their pathogenesis.

 In the future, a more detailed classification of epileptic encephalopathic genotypes will improve the accuracy of risk assessment and genetic counseling. M

oreover, all these developments could yield unexpected therapeutic applications such as gene therapy or antiepileptic drugs “tailored” to the specific patient through specific genetic markers or targets.

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