The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy
The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy
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DOI：
10.1038/ejhg.2012.156
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发表时间：
2013-03-01
影响因子：
5.2
通讯作者：
Christodoulou, John
中科院分区：
文献类型：
--
作者：
Fehr, Stephanie;Wilson, Meredith;Christodoulou, John
临床对CDKL5疾病的了解仍然有限，大多数信息来自个别中心的小患者群体。本研究使用大量国际数据收集来描述CDKL5疾病的临床特征，并与Rett综合征（Rh）进行比较。细胞周期蛋白依赖性激酶样5 （CDKL5）突变个体（n=86）和MECP2突变女性（n=920）的信息来自InterRett数据库。检查了CDKL5患者的现有照片，以确定其畸形特征。CDKL5患者符合最近的非典型Rh T新标准的比例被确定。采用Logistic回归和时间-事件分析比较MECP2和CDKL5突变患者ret样特征的发生情况。大多数CDKL5突变个体从出生起就有严重的发育迟缓，3个月前癫痫发作，并具有类似的非畸形特征。不到四分之一的患者符合早发性癫痫变异Rh的标准。癫痫发作和睡眠障碍比MECP2突变更常见，而退化和脊柱弯曲的特征则不太常见。CDKL5疾病表现出独特的临床特征和微妙的面部、肢体和手部表型，这可能有助于与其他早发性脑病的区分。尽管CDKL5基因突变已被描述为与早发性RTT变异相关，但在我们的研究中，大多数不符合这些标准。因此，CDKL5疾病应该被认为是单独的RTT，而不是另一种变体。欧洲人类遗传学杂志（2013）21,266 -273；doi: 10.1038 / ejhg.2012.156;2012年8月8日在线发布
The clinical understanding of the CDKL5 disorder remains limited, With most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (Rh). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical Rh T was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant Rh. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant. European Journal of Human Genetics (2013) 21, 266-273; doi:10.1038/ejhg.2012.156; published online 8 August 2012