All patients with KCNQ3-related disorders must undergo in-depth neurological examination and developmental evaluation. Cognitive and neuropsychological testing are recommended. Video-EEG monitoring, including sleep-EEG monitoring, and brain MRI imaging should be performed.
Family history should be obtained. Knowing that penetrance of loss-of-function variants is incomplete, even an unaffected parent may carry the pathogenic variant. Thereby, genetic testing of the parents is recommended.
Self-limiting (familial) neonatal epilepsy (S(F)NE), self-limiting (familial) infantile epilepsy (S(F)IE) and KCNQ3-developmental and epileptic encephalopathy (DEE) are caused by loss-of-function variants. Sodium channel blockers (f.e. fosphenytoin and carbamazepine) are recommended as first-line treatment to control neonatal seizures. While it has been suggested that early effective treatment improves cognitive outcome, subsequent neurodevelopment remains poor in KCNQ3-DEE patients. Further DEE-management should include physiotherapy, speech therapy, and behavioral therapy.
KCNQ3-encephalopathy without neonatal epilepsy is mostly caused by gain-of-function variants and needs different therapeutic approaches. Responses to standard anti-seizure medication has shown to be variable: some beneļ¬ts were reported, but no worsening was seen when the anti-seizure medications were discontinued. Treatment with high-dose oral diazepam or corticosteroids showed reduction of the sleep-activated spikes on EEG in some patients, but with inconsistent effects on behavior. Targeted treatment for KCNQ3 gain-of-function patients have not emerged to date. Further management should include physiotherapy, speech therapy, and behavioral therapy.
KCNQ3 patient and variant registry
The RIKEE project (Rational Intervention for KCNQ2/3 Epileptic Encephalopathy):
https://www.rikee.org/