Three cases of progressive myoclonic epilepsy caused by KCNC1 gene mutations and literature review / 中华实用儿科临床杂志

ABSTRACT

Objective@#To summarize the clinical phenotype and genotype features of 3 children with progre-ssive myoclonic epilepsy (PME) caused by KCNC1 gene mutations, and to review the related literatures.@*Methods@#The phenotype and genotype of 3 children with KCNC1 mutations in the Department of Pediatrics, Peking University First Hospital from October 2016 to January 2019 were analyzed.The 25 patients with KCNC1 mutations which had been reported internationally were also collected and analyzed.@*Results@#Three children in this study were identified with KCNC1 de novo mutations, in which 2 children were identified with c. 959G>A (p.Arg320His) mutation, and 1 child with c. 1262C>T (p.Ala421Val) mutation.The clinical features of 3 children were consistent with PME, and the seizure onset ages were 3 months, 10 years and 11 years, respectively.Three children all had myoclonic seizures, among whom 1 child had generalized tonic-clonic seizure and 2 children had focal seizures.Three children all had intellectual and/or motor development delay.The electroencephalograph showed generalized spike and waves or polyspike and waves in 3 children, and focal discharge in 2 children.The brain imaging of 3 children was normal.The last follow-up ages were 3 years old, 13 years old and 12 years old, respectively.Until March 2019, there were 25 cases with KCNC1 gene mutations reported internationally.Including 3 patients in this study, there were 28 patients in total, of which 25 patients were diagnosed with PME.In these 25 patients, 24 patients were identified with p. Arg320His variant in the transmembrane area, 1 patient was identified with p. Ala421Val variant in the transmembrane area.The remaining 3 patients were only found with psychomotor developmental delay without seizures, and they were identified with p. Arg339X variant in the intracellular area.In the 28 patients, 16 cases received cranial imaging data, in which 12 patients had ce-rebellar atrophy and 4 cases were normal.Of the 28 patients, 18 cases were mentally retarded, 27 cases were development retardation or retrogression among whom 9 cases could not walk independently.Ten patients were over 30 years old when reported, and only 1 patient died of pneumonia and respiratory failure at 63 years old.@*Conclusions@#KCNC1 gene mutation mainly leads to PME phenotype, and a few patients can only show mental retardation.p.Arg320His is the most common variant of KCNC1 gene.The variants in different structural regions result in different clinical phenotypes, and variants in the transmembrane region can lead to severer clinical phenotypes.The 3 patients with KCNC1 gene mutations in this study are firstly reported cases in China.