CDKL5综合征7例病例报告

熊 娟 彭 镜 段浩林 陈施梦 尹 飞

1 病例资料

表1 7例CDKL5患儿临床资料

7例患儿起病年龄为22 d至8月龄，中位年龄2月龄。就诊年龄为1月龄至8月龄，中位年龄2月龄。病初发作形式多单一，例3～6表现为部分性发作、例1～4和7为强直发作，随病情进展7例发作形式、发作频次均逐渐增多，均有痉挛发作表现，例1、3和7肌阵挛发作也较为常见，例3在4岁7月转化为Lennox-Gastaut综合征。例7在出现抽搐前即有精神运动发育落后，表现为3月龄竖头不稳，6月龄不能独坐，余6例患儿在起病后出现精神运动发育迟滞。7例均有幼稚面容，例1、2、6和7有异常面容的表现；例4和7有明显头围增长进行减速；例2、5和7有眼球异常运动(斜视、眼球震颤)；部分患儿有吐舌头、不自主运动异常行为，伴有拍手等手刻板动作；例1和2四肢肌力低、例1～4和7肌张力低。

图1本文7例患儿CDKL5基因模式图及突变位点

注 A：CDKL5模式图及本文7例患儿基因突变位点[例1：c.278dupA (p.E93fs)；例2：c.401G>C (p.G134P)；例3：c.1110del C (p.E370fs)；例4：c.58G>C (p.G20R)；例5：c.464G>A (p.G155D)；例6：c.160-163del (p.K54fs)；例7：3～8号外显子杂合缺失]；B：CDKL5突变位点分组标准及本文7例患儿分组(a组：aa172前的截短突变致编码的蛋白无功能/CDKL5整体缺失；b组：激酶区域内的错义/框内突变；c组：aa172～aa781之间的截短突变；d组：aa781(不包含aa781)的截短突变

2 讨论

起调节表达作用，可以调节其激酶活性和核酸定位[17，18]。Fehr研究团队在既往CDKL5研究成果的基础上，结合国际CDKL5综合征数据库的临床数据，在2015年首次提出将CDKL5突变分为4种类型(见图1)：①第172个氨基酸前出现截短突变导致催化区域功能丧失或整个基因缺失；②催化区域内的错义突变或框内突变(如缺失导致一部分激酶区域功能丧失但其后的蛋白编码完整)；③第172～781个氨基酸之间的截短突变，包括移码突变、无义突变等突变类型导致C末端区域丢失但仍有激酶活性；④第781个氨基酸以后的截短突变，保留了激酶活性及大部分C端区域。在此分组基础上，近年来研究表明，D组的CDKL5综合征患儿智力发育较其他组别好，在大运动能区上更可能独站或独走，言语能区上更可能有语言表达发育[19，20]。本文报告的7个突变位点可应用相同分组原则，例1、6和7的突变属A组，病例2、4和5的突变属B组，病例3的突变属C组。结合Fehr等的研究结果，这也解释了本文患儿智力发育均较差的原因。

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