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

doi:10.11852/zgetbjzz2018-26-04-24

Abstract

Abstract: 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 of 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 conducted.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 karyotype 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 related microdeletion/repetition is one of the main genetic causes of unknown GDD patients.Routine G banding karyotype analysis combined with CMA for patients with unexplained GDD will be helpful for the etiology diagnosis,thereby providing evidence for genetic counseling of their families,recurrence risk assessment and prenatal diagnosis.

Key words: global developmental delay, pathogeny, routine G banding karyotype analysis, chromosomal microarray analysis, copy number variations

摘要： 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。

关键词: 全面性发育延迟, 病因, 常规染色体核型, 染色体微阵列, 基因组拷贝数变异

CLC Number:

R179

ZHANG Duan-Xiu, PENG Gui-lan, HU Shu-Xiang. Clinical and chromosome analysis of 92 cases of children with unexplained global developmental delay[J]. journal1, 2018, 26(4): 433-436.

张端秀, 彭桂兰, 胡恕香. 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[J]. 中国儿童保健杂志, 2018, 26(4): 433-436.

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URL: https://manu41.magtech.com.cn/Jwk_zgetbjzz/EN/10.11852/zgetbjzz2018-26-04-24

https://manu41.magtech.com.cn/Jwk_zgetbjzz/EN/Y2018/V26/I4/433

References

[1] 周园,刘振寰,章马兰,等.早期中西医综合干预对不同胎龄全面性发育迟缓患儿的疗效研究[J].中国儿童保健杂志2017,25,(6):643-645.
[2] Ropers HH.Genetics of intellectual disability[J].Curr Opin Genet Dev,2008,18(3):241-250.
[3] Manning M,Hudgins L.Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities[J].Genet Med,2010,12(11):742-745.
[4] Scott SA,CohenN,BrandtT,et al.Detection of low-level mosaicism and placental mosaicism by oligonucleotide array comparative genomic hybridization[J].Genet Med,2010,12(2):85-92.[J].Genet Med,2010,12(2):85-92.
[5] South ST,LeeC,LambAN,et al.ACMG Standards and Guidelines for constitutional cytogenomicmircoarray analysis including postnatal and prenatal applicacations:revision 2013[J].Genet Med,2013,15(11):901-909.
[6] Palmer EE,PetersGB,Mowat D.Chromosome microarray in Australia:a guide for paediatricians[J].J Paediatr Child Health,2012,48(2):E59-67.
[7] Dawson,AJ,ChernosJ,McGowan-Jordan J,et al.CCMG guidelines:prenatal and postnatal diagnostic testing for uniparental disomy[J].Clin Genet,2011,79(2):118-124.
[8] Heilstedt HA,Ballif BC,Howard LA,et al.Population data suggest that deletions of 1p36 are a relatively common chromosome abnormality[J].Clinical Genetics,2003,64(4):310-316.
[9] Chen CP,Chen M,Su YN,et al.Chromosome lp36 deletion syndrome:prenatal diagnosis,molecular cytogenetic characterization and fetal ultrasound findings[J].Taiwan J Obstet Gynecol,2010,49(4):473-480.
[10] Puiu I,Stoica A,Sosoi S,et al.Terminal deletion 2q37.3 in a patient wit Klippel-Trenaunay-Weber syndrome[J].Fetal Pediatr Pathol,2013,32(5):351-356.
[11] Villavicencio-Lorini P,Klopocki E,Trimborn M,et al.Phenotypic variant of Brachydactyly-mental retardation syndrome in a family with an inherited interstitial 2q37.3 microdeletion including HDAC4[J].Eur J Hum Genet,2013,21(7):743-748.
[12] Cody JD,Hasi M,Soileau B,et al.Establishing a reference group for distal 18 q-:clinical description and molecular basis[J].Hum Genet,2014,133(2):199-209.
[13] van Trier DC,Feenstra I,Bot P,et al.Cardiac anomalies in individuals with the 18q deletion syndrome; report of a child with Ebstein anomaly and review of the literature[J].Eur J Med Genet,2013,56(8):426-431.
[14] Dolcetti A,Silversides CK,Marshall CR,et al.lq21.1 Microduplication expression in adults[J].Genet Med,2013,15(4):289.
[15] Digilio MC,Bernardini L,Consoli F,et al.Congenital heart defects in recurrent reciprocal lq21.1 deletion and duplication syndromes:rare association with pulmonary valve stenosis[J].Eur J Med Genet,2013,56(3):144-149.
[16] Rosenfeld JA,Traylor RN,Schaefer GB,et al,Proximal microdeletion and microduplications of lq21.1 contribute to variable abnormal phenotypes[J].Eur J Hum Genet,2012,20(7):754-761.