KCNQ2 related early-onset epileptic encephalopathies in Chinese children.
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.
['Fang|Zhi-Xu|ZX|', 'Zhang|Min|M|', 'Xie|Ling-Ling|LL|', 'Jiang|Li|L|', 'Hong|Si-Qi|SQ|', 'Li|Xiu-Juan|XJ|', 'Hu|Yue|Y|', 'Chen|Jin|J|']
D000595:Amino Acid Sequence D044466:Asians D001927:Brain Diseases D004569:Electroencephalography D004827:Epilepsy D005260:Female D005500:Follow-Up Studies D006801:Humans D007223:Infant D007231:Infant, Newborn D051658:KCNQ2 Potassium Channel D008297:Male D020125:Mutation, Missense D017433:Protein Structure, Secondary D012189:Retrospective Studies
KCNQ2 Early-onset epileptic encephalopathies Phenotype Genotype China