PDF(Pubmed)
Abstract：
OBJECTIVE: Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) are associated with a wide spectrum of clinical presentations. Early-onset epileptic encephalopathy (EOEE) is the most recognized phenotype. Here we describe phenotypic features in eight Tunisian patients with CDKL5-related encephalopathy.
METHODS: We included all cases with clinical features consistent with CDKL5-related encephalopathy: infantile epileptic spasm, acquired microcephaly, movement disorders and visual impairment. We collected data about seizure types, electroencephalogram, magnetic resonance imaging, and metabolic analysis. The diagnosis of CDKL5 mutation was made thanks to Sanger sequencing with an ABI PRISM 3100-Avant automated DNA sequencer using a Big Dye Terminator Cycle Sequencing Reaction Kit v1.1. and Next Generation Sequencing (NGS) since the development of a gene panel responsible for DEE within the framework of \"Strengthening the Sfax University Expertise for diagnosis and management of epileptic encephalopathies\".
RESULTS: We collected four boys and four girls aged meanly 6 years old with confirmed mutation on CDKL5 gene. Overall, we identified five de novo CDKL5 mutations including three Frame-shift mutations, one missense mutation, and a splicing variant. The mean age at first seizure onset was 4 months. The first seizure type was infantile epileptic spasm (4/8) followed by tonic (2/8) and myoclonic seizures (2/8). Out of eight cases, four exhibited two stages epileptic course while epilepsy in three other patients progressed on three stages. Regarding development, most cases (6/8) had psychomotor retardation from the start whilst the two others showed psychomotor regression with the onset of seizures. Additional clinical features included visual impairment (7/8), tone abnormalities (7/8), stereotypies (7/8), and acquired microcephaly (6/8).
CONCLUSIONS: Our present report delineates an unusual phenotype of CDKL5-related encephalopathy with male gender predominance and delayed onset epilepsy. It interestingly described new phenotypic features and uncommon benign developmental profiles in boys, different patterns of CDKL5-epilepsy, neuroimaging findings, and CDKL5 mutational spectrum.
METHODS: We included all cases with clinical features consistent with CDKL5-related encephalopathy: infantile epileptic spasm, acquired microcephaly, movement disorders and visual impairment. We collected data about seizure types, electroencephalogram, magnetic resonance imaging, and metabolic analysis. The diagnosis of CDKL5 mutation was made thanks to Sanger sequencing with an ABI PRISM 3100-Avant automated DNA sequencer using a Big Dye Terminator Cycle Sequencing Reaction Kit v1.1. and Next Generation Sequencing (NGS) since the development of a gene panel responsible for DEE within the framework of \"Strengthening the Sfax University Expertise for diagnosis and management of epileptic encephalopathies\".
RESULTS: We collected four boys and four girls aged meanly 6 years old with confirmed mutation on CDKL5 gene. Overall, we identified five de novo CDKL5 mutations including three Frame-shift mutations, one missense mutation, and a splicing variant. The mean age at first seizure onset was 4 months. The first seizure type was infantile epileptic spasm (4/8) followed by tonic (2/8) and myoclonic seizures (2/8). Out of eight cases, four exhibited two stages epileptic course while epilepsy in three other patients progressed on three stages. Regarding development, most cases (6/8) had psychomotor retardation from the start whilst the two others showed psychomotor regression with the onset of seizures. Additional clinical features included visual impairment (7/8), tone abnormalities (7/8), stereotypies (7/8), and acquired microcephaly (6/8).
CONCLUSIONS: Our present report delineates an unusual phenotype of CDKL5-related encephalopathy with male gender predominance and delayed onset epilepsy. It interestingly described new phenotypic features and uncommon benign developmental profiles in boys, different patterns of CDKL5-epilepsy, neuroimaging findings, and CDKL5 mutational spectrum.
摘要：
目的：细胞周期蛋白依赖性激酶样5基因（CDKL5）的突变与广泛的临床表现有关。早发性癫痫性脑病（EOEE）是最公认的表型。在这里，我们描述了8名突尼斯CDKL5相关性脑病患者的表型特征。
方法：我们纳入了临床特征与CDKL5相关脑病一致的所有病例：婴儿癫痫性痉挛，获得性小头畸形,运动障碍和视力障碍。我们收集了癫痫发作类型的数据，脑电图,磁共振成像和代谢分析。CDKL5突变的诊断是由于Sanger测序与ABIPRISM3100-Avant自动DNA测序仪使用大染料终止子循环测序反应试剂盒v1.1。和下一代测序（NGS），因为在“加强Sfax大学诊断和治疗癫痫性脑病的专业知识”的框架内开发了负责DEE的基因小组。
结果：我们收集了4名男孩和4名女孩，年龄平均为6岁，证实了CDKL5基因突变。总的来说,我们鉴定了5个从头CDKL5突变,包括3个Frameshift突变;一个错义突变和一个剪接变体。首次发作的平均年龄为4个月。第一癫痫发作类型是婴儿癫痫性痉挛（4/8），其次是强直性（2/8）和肌阵挛性癫痫发作（2/8）。在8个案例中，4例表现出两个阶段的癫痫病程，而其他3例患者的癫痫进展为三个阶段。关于发展，大多数病例（6/8）从一开始就有精神运动发育迟缓，而另外两个病例随着癫痫发作而表现出精神运动消退。其他临床特征包括视力障碍（7/8），音调异常（7/8），刻板印象（7/8）和获得性小头畸形（6/8）。
结论：我们的报告描述了CDKL5相关脑病的一个不寻常的表型，男性占主导地位，迟发性癫痫。它有趣地描述了男孩的新表型特征和罕见的良性发育特征，CDKL5-癫痫的不同模式，神经影像学发现和CDKL5突变谱。
方法：我们纳入了临床特征与CDKL5相关脑病一致的所有病例：婴儿癫痫性痉挛，获得性小头畸形,运动障碍和视力障碍。我们收集了癫痫发作类型的数据，脑电图,磁共振成像和代谢分析。CDKL5突变的诊断是由于Sanger测序与ABIPRISM3100-Avant自动DNA测序仪使用大染料终止子循环测序反应试剂盒v1.1。和下一代测序（NGS），因为在“加强Sfax大学诊断和治疗癫痫性脑病的专业知识”的框架内开发了负责DEE的基因小组。
结果：我们收集了4名男孩和4名女孩，年龄平均为6岁，证实了CDKL5基因突变。总的来说,我们鉴定了5个从头CDKL5突变,包括3个Frameshift突变;一个错义突变和一个剪接变体。首次发作的平均年龄为4个月。第一癫痫发作类型是婴儿癫痫性痉挛（4/8），其次是强直性（2/8）和肌阵挛性癫痫发作（2/8）。在8个案例中，4例表现出两个阶段的癫痫病程，而其他3例患者的癫痫进展为三个阶段。关于发展，大多数病例（6/8）从一开始就有精神运动发育迟缓，而另外两个病例随着癫痫发作而表现出精神运动消退。其他临床特征包括视力障碍（7/8），音调异常（7/8），刻板印象（7/8）和获得性小头畸形（6/8）。
结论：我们的报告描述了CDKL5相关脑病的一个不寻常的表型，男性占主导地位，迟发性癫痫。它有趣地描述了男孩的新表型特征和罕见的良性发育特征，CDKL5-癫痫的不同模式，神经影像学发现和CDKL5突变谱。
