| Missense variants in the pore domain | Associated with more severe seizure phenotypes and poorer developmental outcomes |
| Variants in the voltage-sensing domain | Show variable severity |
| Truncating variants | Generally associated with severe phenotypes but may have slightly better developmental outcomes than some missense variants |
| Residual M-current | The degree of residual channel function correlates with clinical severity |
| KCNQ3 upregulation | During the first 1–2 years of life, KCNQ3 expression increases substantially, allowing the formation of more KCNQ2:KCNQ3 heterotetramers that partially restore M-current |
| Other potassium channels | Upregulation of other potassium channel families (e.g., SK channels, Kv1 family) can provide additional compensatory mechanisms |
| Synaptic pruning and circuit refinement | Normal developmental processes can reduce network hyperexcitability even without pharmacological intervention |
| Developmental critical periods | Seizure susceptibility may be highest during specific developmental windows when excitatory processes dominate |
| Databases | OMIMOrphanetClinicalTrialsPubMed |