Segel Reeval, Ben-Pazi Hilla, Zeligson Sharon, Fatal-Valevski Aviva, Aran Adi, Gross-Tsur Varda, Schneebaum-Sender Nira, Shmueli Dorit, Lev Dorit, Perlberg Shira, Blumkin Luba, Deutsch Lisa, Levy-Lahad Ephrat
From the Medical Genetics Institute (R.S., S.Z., S.P., E.L.-L.) and Neuropediatric Unit (H.B.-P., A.A., V.G.-T.), Shaare Zedek Medical Center, Jerusalem; Pediatric Neurology Unit (A.F.-V., N.S.-S.), Dana Children's Hospital, Tel Aviv; Jerusalem Child Development Center (D.S.), Clalit, Jerusalem; Metabolic-Neurogenetic Clinic (D.L., L.B.), Wolfson Medical Center, Holon; and Biostatistical Consulting (L.D.), BioStats, Israel.
Neurology. 2015 Apr 21;84(16):1660-8. doi: 10.1212/WNL.0000000000001494. Epub 2015 Mar 27.
To determine the prevalence and characteristics of copy number variations (CNVs) in children with cerebral palsy (CP) of unknown etiology, comprising approximately 20% of the CP population.
Fifty-two participants (age 10.5 ± 7.8 years; Gross Motor Function Classification System scale 2.8 ± 1.3) with nonprogressive pyramidal and/or extrapyramidal signs since infancy and no identified etiology were enrolled. Individuals with evidence of acquired causes were excluded. Participants underwent neurologic and clinical genetic examinations before the genomic testing. Chromosomal microarray analysis to detect CNVs was performed using the Affymetrix platform. CNVs identified were classified as pathogenic, likely pathogenic, likely benign, or benign. Only pathogenic and likely pathogenic CNVs were defined as clinically significant.
Thirty-nine CNVs were found in 25 of 52 participants (48%). Sixteen participants (31%) had clinically significant CNVs: 10 pathogenic and 6 likely pathogenic, of which 7 were not previously associated with motor disability. Nine participants had likely benign CNVs. Clinically significant CNVs were more frequently de novo (12/16; p < 0.001) including in 5 of 8 individuals who had a first- or second-degree relative with a major neurologic disorder. Dysmorphic features and nonmotor comorbidities were more prevalent in individuals with clinically significant CNVs (p < 0.05 for both).
CNVs, most frequently de novo, are common in individuals with cryptogenic CP. We recommend CNV testing in individuals with CP of unknown etiology.
确定病因不明的脑瘫（CP）儿童中拷贝数变异（CNV）的患病率及特征，此类儿童约占脑瘫人群的20%。
纳入52名自婴儿期起出现非进行性锥体束和/或锥体外系体征且病因未明的参与者（年龄10.5±7.8岁；粗大运动功能分类系统量表评分为2.8±1.3）。排除有后天病因证据的个体。参与者在进行基因组检测前接受了神经学和临床遗传学检查。使用Affymetrix平台进行染色体微阵列分析以检测CNV。所鉴定的CNV被分类为致病性、可能致病性、可能良性或良性。仅致病性和可能致病性CNV被定义为具有临床意义。
52名参与者中有25名（48%）发现了39个CNV。16名参与者（31%）具有临床意义的CNV：10个致病性和6个可能致病性，其中7个以前未与运动障碍相关。9名参与者有可能良性的CNV。具有临床意义的CNV更常为新发（12/16；p<0.001），包括8名有一级或二级亲属患有主要神经系统疾病的个体中的5名。畸形特征和非运动合并症在具有临床意义的CNV个体中更为普遍（两者p均<0.05）。
CNV在病因不明的脑瘫个体中很常见，且最常为新发。我们建议对病因不明的脑瘫个体进行CNV检测。
