Yoon G, Quitania L, Kramer J H, Fu Y H, Miller B L, Ptácek L J
Department of Pediatrics, Division of Medical Genetics, University of California, San Francisco 94158, USA.
Neurology. 2006 Jun 13;66(11):1703-10. doi: 10.1212/01.wnl.0000218214.64942.64.
The Andersen-Tawil syndrome (ATS) is a potassium ion channelopathy caused by mutations in the KCNJ2 gene. It is characterized by periodic paralysis, cardiac arrhythmias, and distinctive features; the effect of KCNJ2 mutations on the CNS has never been studied.
To define a potential CNS phenotype in ATS using standardized methods.
Ten subjects with KCNJ2 mutations and their unaffected siblings were evaluated at the University of California San Francisco General Clinical Research Center. A comprehensive battery of neurocognitive tests was administered to ATS subjects and their unaffected siblings, followed by pairwise analysis of the resultant differences in scores. An EEG was obtained for all ATS subjects.
There was no EEG evidence of subclinical seizure activity in any subject. ATS subjects universally had more school difficulties than their siblings, despite similar IQ between the two groups. On formal neurocognitive testing, there was no difference between ATS subjects and their siblings on tests of verbal and visual memory. Assessment of executive functioning revealed ATS subjects scored 1.93 points lower than their siblings on tests of Design Fluency (95% CI -3.46, 0.01; p = 0.052) and made 1.9 more errors (95% CI 0.46, 2.54; p = 0.005). Subjects with ATS scored an average of 5 points lower than their siblings on tests of matrix reasoning (95% CI -8.67, -1.33; p = 0.008). On tests of general ability, ATS subjects achieved much lower scores than their siblings, with an average difference of 9.13 points for reading (95% CI -12.46, 3.21; p = 0.056) and 23.4 points for mathematics (95% CI -42.53, -4.22; p = 0.017).
Mutations in KCNJ2 are associated with a distinct neurocognitive phenotype, characterized by deficits in executive function and abstract reasoning.
安徒生-陶威尔综合征（ATS）是一种由KCNJ2基因突变引起的钾离子通道病。其特征为周期性麻痹、心律失常及独特体征；KCNJ2突变对中枢神经系统（CNS）的影响尚未得到研究。
采用标准化方法确定ATS潜在的中枢神经系统表型。
10名携带KCNJ2突变的受试者及其未患病的兄弟姐妹在加利福尼亚大学旧金山分校综合临床研究中心接受评估。对ATS受试者及其未患病的兄弟姐妹进行了一系列全面的神经认知测试，随后对所得分数差异进行成对分析。所有ATS受试者均进行了脑电图检查。
所有受试者的脑电图均无亚临床癫痫活动证据。尽管两组智商相似，但ATS受试者在学业上普遍比其兄弟姐妹困难更多。在正式的神经认知测试中，ATS受试者与其兄弟姐妹在言语和视觉记忆测试方面没有差异。执行功能评估显示，在设计流畅性测试中，ATS受试者得分比其兄弟姐妹低1.93分（95%CI -3.46, 0.01；p = 0.052），错误多1.9个（95%CI 0.46, 2.54；p = 0.005）。在矩阵推理测试中，ATS受试者得分平均比其兄弟姐妹低5分（95%CI -8.67, -1.33；p = 0.008）。在一般能力测试中，ATS受试者得分远低于其兄弟姐妹，阅读平均差异为9.13分（95%CI -12.46, 3.21；p = 0.056），数学平均差异为23.4分（95%CI -42.53, -4.22；p = 0.017）。
KCNJ2突变与一种独特的神经认知表型相关，其特征为执行功能和抽象推理缺陷。
