PDF(Pubmed)
Abstract：
Exome sequencing is a first-tier diagnostic test for individuals with neurodevelopmental disorders, including intellectual disability/developmental delay and autism spectrum disorder; however, this recommendation does not include cerebral palsy.
To evaluate if the diagnostic yield of exome or genome sequencing in cerebral palsy is similar to that of other neurodevelopmental disorders.
The study team searched PubMed for studies published between 2013 and 2022 using cerebral palsy and genetic testing terms. Data were analyzed during March 2022.
Studies performing exome or genome sequencing in at least 10 participants with cerebral palsy were included. Studies with fewer than 10 individuals and studies reporting variants detected by other genetic tests were excluded. Consensus review was performed. The initial search identified 148 studies, of which 13 met inclusion criteria.
Data were extracted by 2 investigators and pooled using a random-effects meta-analysis. Incidence rates with corresponding 95% CIs and prediction intervals were calculated. Publication bias was evaluated by the Egger test. Variability between included studies was assessed via heterogeneity tests using the I2 statistic.
The primary outcome was the pooled diagnostic yield (rate of pathogenic/likely pathogenic variants) across studies. Subgroup analyses were performed based on population age and on the use of exclusion criteria for patient selection.
Thirteen studies were included consisting of 2612 individuals with cerebral palsy. The overall diagnostic yield was 31.1% (95% CI, 24.2%-38.6%; I2 = 91%). The yield was higher in pediatric populations (34.8%; 95% CI, 28.3%-41.5%) than adult populations (26.9%; 95% CI, 1.2%-68.8%) and higher among studies that used exclusion criteria for patient selection (42.1%; 95% CI, 36.0%-48.2%) than those that did not (20.7%; 95% CI, 12.3%-30.5%).
In this systematic review and meta-analysis, the genetic diagnostic yield in cerebral palsy was similar to that of other neurodevelopmental disorders for which exome sequencing is recommended as standard of care. Data from this meta-analysis provide evidence to support the inclusion of cerebral palsy in the current recommendation of exome sequencing in the diagnostic evaluation of individuals with neurodevelopmental disorders.
To evaluate if the diagnostic yield of exome or genome sequencing in cerebral palsy is similar to that of other neurodevelopmental disorders.
The study team searched PubMed for studies published between 2013 and 2022 using cerebral palsy and genetic testing terms. Data were analyzed during March 2022.
Studies performing exome or genome sequencing in at least 10 participants with cerebral palsy were included. Studies with fewer than 10 individuals and studies reporting variants detected by other genetic tests were excluded. Consensus review was performed. The initial search identified 148 studies, of which 13 met inclusion criteria.
Data were extracted by 2 investigators and pooled using a random-effects meta-analysis. Incidence rates with corresponding 95% CIs and prediction intervals were calculated. Publication bias was evaluated by the Egger test. Variability between included studies was assessed via heterogeneity tests using the I2 statistic.
The primary outcome was the pooled diagnostic yield (rate of pathogenic/likely pathogenic variants) across studies. Subgroup analyses were performed based on population age and on the use of exclusion criteria for patient selection.
Thirteen studies were included consisting of 2612 individuals with cerebral palsy. The overall diagnostic yield was 31.1% (95% CI, 24.2%-38.6%; I2 = 91%). The yield was higher in pediatric populations (34.8%; 95% CI, 28.3%-41.5%) than adult populations (26.9%; 95% CI, 1.2%-68.8%) and higher among studies that used exclusion criteria for patient selection (42.1%; 95% CI, 36.0%-48.2%) than those that did not (20.7%; 95% CI, 12.3%-30.5%).
In this systematic review and meta-analysis, the genetic diagnostic yield in cerebral palsy was similar to that of other neurodevelopmental disorders for which exome sequencing is recommended as standard of care. Data from this meta-analysis provide evidence to support the inclusion of cerebral palsy in the current recommendation of exome sequencing in the diagnostic evaluation of individuals with neurodevelopmental disorders.
摘要：
未经证实：外显子组测序是针对神经发育障碍患者的一级诊断测试，包括智力障碍/发育迟缓和自闭症谱系障碍；然而，该建议不包括脑瘫.
UNASSIGNED：评估脑瘫中外显子组或基因组测序的诊断产量是否与其他神经发育障碍相似。
UNASSIGNED：研究小组使用脑瘫和基因检测术语搜索了PubMed在2013年至2022年之间发表的研究。数据在2022年3月进行了分析。
UNASSIGNED：在至少10名脑瘫患者中进行外显子组或基因组测序的研究被纳入。少于10个人的研究和报告通过其他基因测试检测到的变异的研究被排除在外。进行了共识性审查。最初的搜索确定了148项研究，其中13人符合纳入标准。
UNASSIGNED：数据由2名研究者提取，并使用随机效应荟萃分析进行汇总。计算相应95%CI和预测区间的发生率。通过Egger测试评估出版偏差。通过使用I2统计量的异质性测试评估纳入研究之间的差异。
UNASSIGNED：主要结果是所有研究的合并诊断率（致病性/可能的致病性变异率）。亚组分析基于人群年龄和使用排除标准进行患者选择。
UNASSIGNED：纳入了13项研究，包括2612名脑瘫患者。总诊断率为31.1%（95%CI，24.2%-38.6%；I2=91%）。儿科人群的产率（34.8％；95％CI，28.3％-41.5％）高于成人人群（26.9％；95％CI，1.2％-68.8％），并且在使用排除标准进行患者选择的研究中（42.1％；95％CI，36.0％-48.2％）高于未选择标准的研究（20.7％；95％CI，12.3％-30.5％）。
未经评估：在本系统综述和荟萃分析中，脑瘫的基因诊断率与其他神经发育障碍相似,而外显子组测序被推荐为治疗标准.这项荟萃分析的数据提供了证据，支持将脑瘫纳入当前建议的外显子组测序在神经发育障碍患者的诊断评估中。
UNASSIGNED：评估脑瘫中外显子组或基因组测序的诊断产量是否与其他神经发育障碍相似。
UNASSIGNED：研究小组使用脑瘫和基因检测术语搜索了PubMed在2013年至2022年之间发表的研究。数据在2022年3月进行了分析。
UNASSIGNED：在至少10名脑瘫患者中进行外显子组或基因组测序的研究被纳入。少于10个人的研究和报告通过其他基因测试检测到的变异的研究被排除在外。进行了共识性审查。最初的搜索确定了148项研究，其中13人符合纳入标准。
UNASSIGNED：数据由2名研究者提取，并使用随机效应荟萃分析进行汇总。计算相应95%CI和预测区间的发生率。通过Egger测试评估出版偏差。通过使用I2统计量的异质性测试评估纳入研究之间的差异。
UNASSIGNED：主要结果是所有研究的合并诊断率（致病性/可能的致病性变异率）。亚组分析基于人群年龄和使用排除标准进行患者选择。
UNASSIGNED：纳入了13项研究，包括2612名脑瘫患者。总诊断率为31.1%（95%CI，24.2%-38.6%；I2=91%）。儿科人群的产率（34.8％；95％CI，28.3％-41.5％）高于成人人群（26.9％；95％CI，1.2％-68.8％），并且在使用排除标准进行患者选择的研究中（42.1％；95％CI，36.0％-48.2％）高于未选择标准的研究（20.7％；95％CI，12.3％-30.5％）。
未经评估：在本系统综述和荟萃分析中，脑瘫的基因诊断率与其他神经发育障碍相似,而外显子组测序被推荐为治疗标准.这项荟萃分析的数据提供了证据，支持将脑瘫纳入当前建议的外显子组测序在神经发育障碍患者的诊断评估中。
