Gene

Neuroscience

Biology

Missense mutation

Channelopathy

Psychiatry

Autism

Genetics

Pediatrics

Bioinformatics

Psychology

Epilepsy

Intellectual disability

Chorea

Internal medicine

Medicine

Dravet syndrome

Disease

Autism spectrum disorder

Loss function

Phenotype

Epilepsia

Pathogenic variants in the SCN2A gene are associated with a variety of neurodevelopmental phenotypes, defined in recent years through multicenter collaboration. Phenotypes include benign (self-limited) neonatal and infantile epilepsy and more severe developmental and epileptic encephalopathies also presenting in early infancy. There is increasing evidence that an important phenotype linked to the gene is autism and intellectual disability without epilepsy or with rare seizures in later childhood. Other associations of SCN2A include the movement disorders chorea and episodic ataxia. It is likely that as genetic testing enters mainstream practice that new phenotypic associations will be identified. Some missense, gain of function variants tend to present in early infancy with epilepsy, whereas other missense or truncating, loss of function variants present with later-onset epilepsies or intellectual disability only. Knowledge of both mutation type and functional consequences can guide precision therapy. Sodium channel blockers may be effective antiepileptic medications in gain of function, neonatal and infantile presentations.

Phenotypic spectrum and genetics of <i> <scp>SCN</scp> 2A </i> ‐related disorders, treatment options, and outcomes in epilepsy and beyond

Phenotypic spectrum and genetics of SCN 2A ‐related disorders, treatment options, and outcomes in epilepsy and beyond