Pathogenic variants in SCN2A are associated with various neurological disorders including epilepsy, autism spectrum disorder and intellectual disability.
The aim of the study was to explore the effect of SCN1A and SCN2A gene polymorphisms on VPA response in the treatment of epilepsy among Chinese patients.
For SCN2A polymorphism c.56 G > A rs17183814, one hundred patients with epilepsy who were receiving lamotrigine in monotherapy and seventy-one age and sex matched healthy controls were genotyped using TaqMan assay.
These findings suggest that impaired cortico-striatal excitatory transmission is a plausible mechanism that triggers epilepsy in Stxbp1 and Scn2a haplodeficient mice.
As far as we are aware our case is the youngest patient with SCN2A mutation treated with KD with complete resolution of epilepsy at an early age and has been seizure free of antiepileptic medications for a long duration.
The purpose of this study was to evaluate the frequency of mosaicism detected by next-generation sequencing in genes associated with epilepsy-related neurodevelopmental disorders.MethodsWe conducted a retrospective analysis of 893 probands with epilepsy who had a multigene epilepsy panel or whole-exome sequencing performed in a clinical diagnostic laboratory and were positive for a pathogenic or likely pathogenic variant in one of nine genes (CDKL5, GABRA1, GABRG2, GRIN2B, KCNQ2, MECP2, PCDH19, SCN1A, or SCN2A).
This study demonstrated a significant association between the <i>SCN1A (3184 AG</i> and <i>GG)</i> and <i>SCN2A (56GA</i> and <i>AA)</i> genotype with CBZ-nonresponsive epilepsy.
SCN2A mutations have been identified in various encephalopathy phenotypes, ranging from benign familial neonatal-infantile seizure (BFNIS) to more severe forms of epileptic encephalopathy such as Ohtahara syndrome or epilepsy of infancy with migrating focal seizure (EIMFS).
The SCN2A gene encoding α2 subunit of the neuronal sodium channel has been reported to be associated with BFNIS, GFES+, Dravet syndrome and some intractable childhood epilepsies.
Integration of biological/pathophysiological contexts to help clarify genotype-phenotype mismatches in monogenetic diseases. Childhood epilepsies associated with SCN2A as a case study.
Our findings broaden the clinical spectrum of SCN2A mutations, which resembles clinical phenotypes of SCN1A mutations by manifesting as fever sensitive seizures, and highlights that SCN2A mutations are an important cause of early-onset epileptic encephalopathies with movement disorders.
Taken together with the previously reported cases, our study suggests that having an extra copy of SCN2A has an effect on epilepsy pathogenesis, causing benign familial infantile seizures which eventually disappear at the age of 1-2 years.
Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy.
We argue that very rare, LoF mutations at SCN2A act in a moderately penetrant manner to increase the risk of developing several neuropsychiatric disorders including seizure disorders, ID, autism and schizophrenia.
Scn2a(Q54) phenotype severity varies depending on the genetic strain background, making it a useful model for identifying and characterizing epilepsy modifier genes.
While a causal role for these mutations cannot be directly established, these findings contribute to growing evidence that mutation of SCN2A is associated with a range of epilepsy phenotypes including severe infantile-onset epilepsy.