Fig. 6: The phenotypic spectrum of SCN2A-related disorders.
From: Functional correlates of clinical phenotype and severity in recurrent SCN2A variants
Pink/red boxes indicate phenotypes associated with gain-of-function (GoF) of the Nav1.2 channel, and blue boxes loss-of-function (LoF) phenotypes; Onset refers to age of seizure onset. The phenotypic groups associated with more severe epilepsies are sometimes grouped as SCN2A developmental and epileptic encephalopathies (gray box), which encompasses both GoF and LoF phenotypes. The early-infantile (EI) phenotypes can be considered a spectrum of clinical severity associated with biophysical GoF. While the later-onset (LO) epilepsy phenotypes and ID/ASD without epilepsy are both associated with LoF, it is not clear whether these represent a spectrum of severity (related to partial or total loss of channel function), or are distinct disorders caused by different mechanisms of channel hypofunction (for example pure LoF vs dominant negative effect).
