关键词: 早发性癫痫脑病；　KCNQ2基因；　突变

Abstract: 　Objective　To investigate the correlation between clinical phenotype and genotype in children with epilepsy associated with KCNQ2 gene mutation. Methods　10 EOEE (early-onset epileptic encephalopathy) patients including a pair of twins with KCNQ2 mutations were studied. Whole-exome sequencing (WES) was performed to identify genetic change and relevant clinical features were collected. Sanger sequencing was performed to confirm variants detected by WES. Clinical features were evaluated by neurological specialists. EEG, MRI and treatment information were collected accordingly. Results　Ten (10) patients with KCNQ2 mutations were reported in our study. WES identified 5 novel KCNQ2 mutations (c.1720_1721delGG, c.185C>T, c.2180A>G, c.2245G>A, c.1164A>T)，and three reported mutations (c.917C>T, c.1687G>A, c.1741C>T) in 10 patients with early-onset epilepsy encephalopathy. In twin patients with stop-gain mutation of c.807G>A, one presented with benign familial neonatal seizures, while the other with EOEE. Five of other six family members of the twins investigated were c.807G> A mutation carriers. Ten patients underwent single-agent or combination therapy with phenobarbital, sodium valproate, topiramate, oxcarbazepine, and levetiracetam. For most patients, the symptoms were improved with less frequent or no seizures. Conclusion　KCNQ2 gene-associated epilepsy is a lineage disease, and KCNQ2 mutations can lead to a variety of clinical phenotypes ranging from the heaviest EOEE to the mildest familial neonatal epilepsy. The type and site distribution of KCNQ2 gene mutations may be associated with clinical phenotypes. Individualized treatment is extremely important for KCNQ2 mutation-related epilepsy.

Key words: 　early onset epilepsy encephalopathy;　KCNQ2 gene;　gene mutations