The advances in neuroimaging and genetics, as well as improved understanding of the role of specific autoantibodies as causal for certain epilepsies, have allowed greater accuracy in diagnosis for many children with epilepsy, potentially opening the door to a precision medicine approach. One example is the potential use of high-dose phenytoin for infants with gain-of-function mutations in the SCN2A channel gene who present with the syndrome of epilepsy of infancy with migrating focal seizures. Another example is resective surgery for focal cortical dysplasia.
Etiologies for epilepsy are divided into 6 subgroups: genetic, structural, metabolic, immune, infectious, and unknown. Sometimes 2 or more subgroups are involved, as in tuberous sclerosis, which is a genetic-structural etiology, or Leigh syndrome, which is a genetic-metabolic etiology.
A genetic etiology is defined by the epilepsy being the direct result of a known or presumed genetic defect, and seizures are the core symptom of the disorder. This category includes the generalized genetic epilepsy syndromes (also known as idiopathic generalized epilepsies), such as childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with tonic-clonic seizures alone, in which there is strong evidence from both family and twin studies of this heritable nature.
Other genetic causes are associated with intellectual disability and poorer prognosis for seizure control, including cyclin-dependent kinase-like 5 (CDKL5), aristaless-related homeobox (ARX) mutations, Dravet syndrome, protocadherin 19 female-limited epilepsies, and Down syndrome. The yield of genetic testing in early-onset epilepsies is very high in both children with or without underlying malformations of cortical development. (34)(35)