All patients with KCNQ2-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 is around 80% in self-limiting familial neonatal epilepsy and mosaicism is described, 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) and KCNQ2-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 treat neonatal seizures. Seizures tend to poorly respond to phenobarbital and levetiracetam. Seizures are more therapy-resistant in KCNQ2-DEE patients and often requires prompt treatment with repeated loads of anti-seizure medication and/or continuous infusions. In S(F)NE low doses of carbamazepine (10mg/kg/day) are generally sufficient. In addition, a randomized, double-blind, placebo-controlled trial with the potassium channel opener retigabine has recently been initiated in children with KCNQ2-DEE with active seizures between the age of 1 months and 6 years (ClinicalTrials.gov Identifier: NCT04639310). While it has been suggested that early effective treatment improves cognitive outcome, cognitive outcome remains poor in KCNQ2-DEE patients. Further DEE-management should include physiotherapy, speech therapy, and behavioral therapy.
KCNQ-encephalopathy without neonatal epilepsy is mostly caused by gain-of-function variants and need different therapeutic approaches. Responses to standard treatments are poor. A partial response of vigabatrin in some patients with non-epileptic myoclonus is reported. In addition, a response to corticosteroid or vigabatrin treatment in patients with infantile spasms has been described. Unlike for KCNQ2 loss-of-function, targeted treatment for KCNQ2 gain-of-function patients have not emerged to date. Further management should include physiotherapy, speech therapy, and behavioral therapy.
Support groups
KCNQ2 Cure: https://www.kcnq2cure.org/
European KCNQ2 association: https://www.europeankcnq2association.com/?lang=en
KCNQ2 patient and variant registry
The RIKEE project (Rational Intervention for KCNQ2/3 Epileptic Encephalopathy): https://www.rikee.org/
KCNQ2