Children's Hospital Colorado, Aurora, Colorado.
Adult and Child Consortium for Health Outcomes Research and Delivery Science, Aurora, Colorado.
Epilepsia. 2019 Aug;60(8):1733-1742. doi: 10.1111/epi.16285. Epub 2019 Jul 16.
The cyclin-dependent kinase like 5 (CDKL5) gene is a known cause of early onset developmental and epileptic encephalopathy, also known as CDKL5 deficiency disorder (CDD). We sought to (1) provide a description of seizure types in patients with CDD, (2) provide an assessment of the frequency of seizure-free periods and cortical visual impairment (CVI), (3) correlate these features with genotype and gender, and (4) correlate these features with developmental milestones.
This is a cohort study of patients with CDD. Phenotypic features were explored and correlated with gene variant grouping and gender. A developmental score was created based on achieving seven primary milestones. Phenotypic variables were correlated with the developmental score to explore markers of better developmental outcomes. Multivariate linear regression was used to account for age at last visit.
Ninety-two patients with CDD were seen during the enrollment period. Eighteen were male (19%); median age at last visit was 5 years (interquartile range = 2.0-11.0). Eighty-one percent of patients developed epileptic spasms, but only 47% of those also had hypsarrhythmia. Previously described hypermotor-tonic-spasms sequence was seen in only 24% of patients, but 56% of patients had seizures with multiple phases (often tonic and spasms). Forty-three percent of patients experienced a seizure-free period ranging from 1 to >12 months, but only 6% were still seizure-free at the last visit. CVI was present in 75% of all CDD patients. None of these features was associated with genotype group or gender. CVI was correlated with reduced milestone achievement after adjusting for age at last visit and a history of hypsarrhythmia.
The most common seizure types in CDD are epileptic spasms (often without hypsarrhythmia) and tonic seizures that may cluster together. CVI is a common feature in CDD and is correlated with achieving fewer milestones.
细胞周期蛋白依赖性激酶样 5（CDKL5）基因是早发性发育性和癫痫性脑病（也称为 CDKL5 缺乏症（CDD））的已知原因。我们旨在：（1）描述 CDD 患者的癫痫发作类型；（2）评估无癫痫发作期和皮质视觉障碍（CVI）的频率；（3）将这些特征与基因型和性别相关联；（4）将这些特征与发育里程碑相关联。
这是一项 CDD 患者的队列研究。探索了表型特征，并将其与基因变异分组和性别相关联。根据实现七个主要里程碑，创建了一个发育评分。将表型变量与发育评分相关联，以探索更好的发育结果的标志物。使用多元线性回归来解释末次就诊时的年龄。
在入组期间共观察到 92 例 CDD 患者。18 例为男性（19%）；末次就诊时的中位年龄为 5 岁（四分位距=2.0-11.0）。81%的患者出现癫痫性痉挛，但只有 47%的患者出现高度不规则性脑电活动。仅 24%的患者出现先前描述的高度运动痉挛序列，但 56%的患者出现多相（常为强直和痉挛）发作。43%的患者经历了 1 至＞12 个月的无癫痫发作期，但只有 6%的患者在末次就诊时仍无癫痫发作。CVI 存在于所有 CDD 患者的 75%中。这些特征均与基因型分组或性别无关。在调整末次就诊时的年龄和高度不规则性脑电活动病史后，CVI 与里程碑的实现减少相关。
CDD 中最常见的癫痫发作类型是癫痫性痉挛（常无高度不规则性脑电活动）和强直发作，这些发作可能聚集在一起。CVI 是 CDD 的常见特征，与实现较少的里程碑有关。
