Zhi-Xu Fang1,2,3,4, Min Zhang2,3,4, Ling-Ling Xie5,6,7,8, Li Jiang1,2,3,4, Si-Qi Hong1,2,3,4, Xiu-Juan Li1,2,3,4, Yue Hu1,2,3,4, Jin Chen1,2,3,4. 1. Department of Neurology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan Er Road, Yuzhong District, Chongqing, 400014, China. 2. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China. 3. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China. 4. Chongqing Key Laboratory of Pediatrics, Chongqing, China. 5. Department of Neurology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan Er Road, Yuzhong District, Chongqing, 400014, China. cqmu_xielingling@126.com. 6. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China. cqmu_xielingling@126.com. 7. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China. cqmu_xielingling@126.com. 8. Chongqing Key Laboratory of Pediatrics, Chongqing, China. cqmu_xielingling@126.com.
Abstract
OBJECTIVE: To study the phenotype, genotype, treatment strategies, and short-term prognosis of Chinese children with KCNQ2 (potassium voltage-gated channel subfamily Q member 2) related early-onset epileptic encephalopathies (KCNQ2-EOEEs) in Southwest China. METHODS: We used targeted next-generation sequencing (NGS) to identify KCNQ2 variants in Chinese patients with EOEEs. And patients with KCNQ2-EOEEs were confirmed after clinical and genetic analyses. We followed them in our cohort and analyzed their clinical data. RESULTS: 122 patients with EOEEs were registered from August 2015 to October 2017, and 78 underwent targeted NGS. Seven among them were confirmed to be caused by pathogenic KCNQ2 variants, 6 of that were de novo and 1 was inherited. The median seizure onset age of the 7 patients was 5 days. Tonic-clonic and tonic seizures were the major seizure types; the electroencephalograms of all patients showed multifocal sharp waves initially. When new seizure types appeared in infancy, the most common type was epileptic spasm. At the last follow-up, seizures persisted in only one patient, and another patient had seizure recurrence. The identified pathogenic KCNQ2 variants introduced amino acid missense changes, or in one instance, frameshift variant, four of which have not been reported. Valproic acid (VPA) was effective as concomitant treatment in three patients, and all patients had intellectual/developmental disabilities (IDDs). CONCLUSIONS: The KCNQ2 missense variant plays an important role in EOEE pathogenesis, and patients with KCNQ2-EOEEs mainly present with intractable seizures and IDDs. Moreover, VPA has potential as an effective therapeutic strategy.
OBJECTIVE: To study the phenotype, genotype, treatment strategies, and short-term prognosis of Chinese children with KCNQ2 (potassium voltage-gated channel subfamily Q member 2) related early-onset epilepticencephalopathies (KCNQ2-EOEEs) in Southwest China. METHODS: We used targeted next-generation sequencing (NGS) to identify KCNQ2 variants in Chinese patients with EOEEs. And patients with KCNQ2-EOEEs were confirmed after clinical and genetic analyses. We followed them in our cohort and analyzed their clinical data. RESULTS: 122 patients with EOEEs were registered from August 2015 to October 2017, and 78 underwent targeted NGS. Seven among them were confirmed to be caused by pathogenic KCNQ2 variants, 6 of that were de novo and 1 was inherited. The median seizure onset age of the 7 patients was 5 days. Tonic-clonic and tonic seizures were the major seizure types; the electroencephalograms of all patients showed multifocal sharp waves initially. When new seizure types appeared in infancy, the most common type was epilepticspasm. At the last follow-up, seizures persisted in only one patient, and another patient had seizure recurrence. The identified pathogenic KCNQ2 variants introduced amino acid missense changes, or in one instance, frameshift variant, four of which have not been reported. Valproic acid (VPA) was effective as concomitant treatment in three patients, and all patients had intellectual/developmental disabilities (IDDs). CONCLUSIONS: The KCNQ2 missense variant plays an important role in EOEE pathogenesis, and patients with KCNQ2-EOEEs mainly present with intractable seizures and IDDs. Moreover, VPA has potential as an effective therapeutic strategy.