不明原因全面性发育迟缓患儿92例临床特征与染色体分析

Clinical and chromosome analysis of 92 cases of children with unexplained global developmental delay

目的探讨不明原因全面性发育迟缓(GDD)患儿临床与遗传学病因,为遗传咨询、同胞的再发风险评估和产前诊断提供理论基础。方法选择不明原因GDD患儿92例,采用常规G显带染色体核型进行分析。若常规G显带染色体核型分析正常,进一步行染色体微阵列技术(CMA)进行全基因组拷贝数变异(CNVs)检测分析致病的拷贝数变异,并分析CNVs与GDD相关性。结果 92例不明原因GDD患儿其染色体结果异常的共有18例(19.6%),其中常规G显带染色体核型分析异常的有11例(12.0%),染色体微阵列分析技术检测异常的有7例(7.6%);共发现7个pCNVs,涉及4个已知综合征,分别为1p36缺失综合征、2q37微缺失综合征、18q缺失综合征、lq21.1微重复综合征。结论常规G显带染色体核型分析及染色体微阵列技术(CMA)能够为不明原因的GDD患者提供明确的病因诊断,为其家庭进行遗传咨询、再发风险评估及产前诊断提供坚实的理论基础。

Objective To explore the clinical and genetic etiology in children with global developmental delay（GDD）, and to provide theoretical basis for the genetic counseling, recurrence risk assessment of sibling and prenatal diagnosis. Methods A total o{ 92 cases of unexplained GDD were selected and analyzed by routine G banding karyotype analysis. If the result of routine G banding karyotype analysis was normal,further lines of chromosomal microarray analysis（CMA） for genome-wide copy number variations （CNVs） detection,analysis of pathogenesis of copy number variation would be conduc- ted. And the correlation between CNVs and GDD was analyzed. Results In this study,there were 18 cases （19.6%） with abnormal chromosomal results of 92 patients with unexplained GDD. Among them, 11 cases （12.0%） showed abnormal kar- yotype analysis results by routine G banding. Seven cases （7.6%） of abnormality in chromosome microarray analysis were detected. 7 pCNVs were found in these 7 cases including 4 known syndromes like 1p36 deletion comprehensive syndrome, 2q37 microdeletion syndrome,18q deletion syndrome,and lq21.1 microdeletion syndrome. Conclusions Gene CNVs relat- ed microdeletion/repetition is one of the main genetic causes of unknown GDD patients. Routine G banding karyotype analy sis combined with CMA for patients with unexplained GDD will be helpful for the etiology diagnosis,thereby providing evi- dence for genetic counseling of their families, recurrence risk assessment and prenatal diagnosis.