ABSTRACT
Objective@#To investigate the genotype and phenotype of children with KCNA2 gene related developmental and epileptic encephalopathy (DEE).@*Methods@#Clinical data including the manifestations and electroencephalogram of 8 children with KCNA2 variants treated in the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were collected and analyzed retrospectively.@*Results@#Among the 8 epileptic patients with KCNA2 variants, 5 were males and 3 were females. The age of onset was from 1 day to 11 months. The age at last follow-up ranged from 4 months to 86 months. Two variants including c.1214C>T (loss-of-function) and c.1120A>G (gain-and loss-of-function) were identified. The variant of c.1214C>T was found in six patients (case 1-6). For these patients, the age of onset was from 5 to 11 months and they were characterized by multiple seizure types. All had focal seizures and had normal development before seizure onset with developmental regression after seizure onset. The first electroencephalogram showed epileptic discharges in Rolandic region in two, epileptic discharges in Rolandic region combined with generalized discharge in one, generalized discharge with posterior predominance in two (combined with or transferred to Rolandic region during the course) and epileptic discharges in posterior region combined with generalized discharge in one. And in 5 of them the Rolandic discharges developed into epileptic electrical status (ESES) during sleep. All the six patients were still treated with a combination of multiple antiepileptic drugs. Two of them had seizure controlled at 80 months and 68 months, respectively. The variant of c.1120A>G were identified in two of eight patients (case 7 and 8) and they had seizure onset on the 1st day after birth. Their epileptic seizures were frequent and difficult to control. They had remarkably developmental delay and microcephaly since birth. One case (case 8) had a wide forehead. They had frequent seizures up to the last follow-up. In case 7, the early electroencephalogram showed epileptic discharges in temporal region, and interictal electroencephalogram at 3 months of age showed multifocal discharge with posterior and temporal region predominance. In case 8, the early electroencephalogram was normal and electroencephalogram showed burst suppression at 2 months of age, and it developed epileptiform discharge in posterior region at 1 year of age.@*Conclusions@#KCNA2 gene variants can lead to DEE with multiple seizures types. Among them, loss-of-function c.1214C>T is the most common, and these patients have seizure onset at infancy with Rolandic discharges tended to develop into to ESES pattern. The variant of c.1120A>G is a gain-of- and loss-of-function variant, patients with c.1120A>G have seizure onset in neonatal period, the phenotype overlaps with the former but is more severe.
ABSTRACT
Episodic ataxia (EA) is a clinically heterogeneous group of disorders that are characterized by recurrent spells of truncal ataxia and incoordination lasting minutes to hours. Most have an autosomal dominant inheritance pattern. To date, 8 subtypes have been defined according to clinical and genetic characteristics, and five genes are known to be linked to EAs. Both EA1 and EA2, which are caused by mutations in KCNA1 and CACNA1A, account for the majority of EA, but many patients with no identified mutations still exhibit EA-like clinical features. Furthermore, genetically confirmed EAs have mostly been identified in Caucasian families. In this article, we review the current knowledge on the clinical and genetic characteristics of EAs. Additionally, we summarize the phenotypic features of the genetically confirmed EA2 families in Korea.
Subject(s)
Humans , Ataxia , Inheritance Patterns , KoreaABSTRACT
Objective:To identify potentially pleiotropic genes for lean body mass ( LBM ) and age at menarche ( AAM).Methods:The discovery sample consisted of 1 692 unrelated female subjects of European ancestry.The replication sample consisted of 801 unrelated female subjects of Han Chinese ancestry.A total of 909,622 single nucleotide polymorphisms (SNPs) were genotyped in both samples with the Affymetrix genome-wide genotyping array SNP 6.0.Bivariate genome-wide association analyses were then performed to the appendicular LBM and AAM.Results: Two SNP rs1860547 and rs11030746 identified by the bivariate GWAS were significant at the genome-wide significance (GWS) level;their P-values were <0.05 after replications.In the upstream of rs1860547, two genes KCNA1 and KCNA5 were found to be important for both LBM and AAM.In the downstream of rs11030746, one gene KCNA4 was found.Univariate GWAS also identified both SNPs to be significant at the GWS level; their P-values were <0.05 after replications.In the upstream of rs1860547 , two genes KCNA1 and KCNA5 are found to be important for LBM.In the downstream of rs11030746 , one gene KCNA4 was found.Conclusion:KCNA1, KCNA4 and KCNA5 are likely to be pleiotropic genes closely related to both LBM and AAM in European females.