胎儿淋巴水囊瘤与染色体异常的相关性研究及妊娠结局分析
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摘要
目的:探讨胎儿颈部淋巴水囊瘤(CCH)与染色体异常的相关性,以及早孕期CCH胎儿的妊娠结局。方法:选取2012年1月1日至2016年6月1日在广州医科大学附属第三医院胎儿医学科门诊行早孕期NT筛查发现CCH的胎儿160例。孕妇均行产前诊断,对染色体及基因芯片结果未见异常的胎儿,建议孕妇于妊娠20～24周接受详细的胎儿III级排畸超声筛查。新生儿随访时间为出生后2～25个月。结果:160例行遗传学诊断的早孕期CCH样本中,染色体核型分析44例,行高分辨CMA分析116例。染色体异常82例,其中最常见的染色体异常为Turner's综合征(31例,33.7%),其次为18三体(24例,26.1%)、21三体(17例,18.5%),13三体7例,染色体平衡易位2例,染色体嵌合1例。基因芯片异常10例,其中6例致病性拷贝数异常。染色体及芯片未见异常的68例中,除10例死胎外,发现超声结构异常18例。染色体、芯片及超声均未见异常且选择继续妊娠的病例中,活产率为98%。截止随访日,活产胎儿暂未发现明显异常。胎儿心脏异常尤其是室间隔缺损在非染色体异常病例中的发生率较高。26例双胎中,约57.7%发现明显染色体异常,染色体检查、芯片及超声检查均未见异常的病例中,选择继续妊娠的4例双胎均活产健康。结论:对于早孕期CCH的预后,需排除常见的染色体异常及致病性拷贝数变异,同时还需结合胎儿排畸超声情况综合判断。如均未见明显异常,且后期未发生胎儿水肿的孤立性淋巴水囊瘤的胎儿出生后预后良好。
Objective:To explore the correlation between fetus cystic lymphangioma and chromosomal abnormalities,and the pregnancy outcomes of the fetuses with cervical cystic hygroma(CCH) of the early pregnancy.Methods:We followed up the fetuses which were diagnosed as CCH during nuchal translucency(NT) screening in the first trimester at Fetal Medicine Department of the Third Affiliated Hospital of Guang Zhou Medical University from Jan.1,2012 to Jun. 6,2016.All the pregnant women carryed out prenatal diagnosis.For fetuses with no abnormalities in chromosome and chromosomal microarray analysis(CMA) results,it was recommended that pregnant women received detailed fetal grade III malformation ultrasound screening at 20～24 weeks of gestation.Neonatal prognosis were followed up to 2 to 25 months after birth.Results:In 160 cases of early pregnancy CCH samples diagnosed by genetics,44 cases were analyzed for chromosome karyotype and 116 cases were analyzed by high-resolution CMA.There were 82 cases of chromosomal abnormalities,the most common chromosomal abnormalities were Turner's syndrome(31 cases,33.7%),followed by 18 trisomy(24 cases,26.1%),21 trisomy(17 cases,18.5%),13 trisomy in 7 cases,there were 2 cases of chromosome balanced translocation and 1 case of chromosome mosaic.There were 10 abnormalities in the CMA,and 6 of them had abnormal pathogenic copy number.Among the 68 cases with no abnormalities in chromosomes and CMA,except for 10 stillbirths,18 cases of abnormal ultrasound structure were found.Among the cases with no abnormalities in chromosome,CMA and ultrasound,the live birth rate was 98% in the cases of continued pregnancy,and no obvious abnormalities were found in the live fetus until the date of follow-up.Fetal heart abnormalities were the most common disease among non-chromosomal abnormalities,especial ventricular septal defects.We found 57.7% obvious chromosomal abnormalities among the 26 twins.Among the twin cases with no abnormalities in chromosome examination,CMA and ultrasound,4 cases of twins without abortion were healthy.Conclusion:If there was no obvious abnormality either chromosome,CMA or ultrasound,and the isolated CCH with no fetal edema in the later stage had a good prognosis after birth.
Objective:To explore the correlation between fetus cystic lymphangioma and chromosomal abnormalities,and the pregnancy outcomes of the fetuses with cervical cystic hygroma(CCH) of the early pregnancy.Methods:We followed up the fetuses which were diagnosed as CCH during nuchal translucency(NT) screening in the first trimester at Fetal Medicine Department of the Third Affiliated Hospital of Guang Zhou Medical University from Jan.1,2012 to Jun. 6,2016.All the pregnant women carryed out prenatal diagnosis.For fetuses with no abnormalities in chromosome and chromosomal microarray analysis(CMA) results,it was recommended that pregnant women received detailed fetal grade III malformation ultrasound screening at 20～24 weeks of gestation.Neonatal prognosis were followed up to 2 to 25 months after birth.Results:In 160 cases of early pregnancy CCH samples diagnosed by genetics,44 cases were analyzed for chromosome karyotype and 116 cases were analyzed by high-resolution CMA.There were 82 cases of chromosomal abnormalities,the most common chromosomal abnormalities were Turner's syndrome(31 cases,33.7%),followed by 18 trisomy(24 cases,26.1%),21 trisomy(17 cases,18.5%),13 trisomy in 7 cases,there were 2 cases of chromosome balanced translocation and 1 case of chromosome mosaic.There were 10 abnormalities in the CMA,and 6 of them had abnormal pathogenic copy number.Among the 68 cases with no abnormalities in chromosomes and CMA,except for 10 stillbirths,18 cases of abnormal ultrasound structure were found.Among the cases with no abnormalities in chromosome,CMA and ultrasound,the live birth rate was 98% in the cases of continued pregnancy,and no obvious abnormalities were found in the live fetus until the date of follow-up.Fetal heart abnormalities were the most common disease among non-chromosomal abnormalities,especial ventricular septal defects.We found 57.7% obvious chromosomal abnormalities among the 26 twins.Among the twin cases with no abnormalities in chromosome examination,CMA and ultrasound,4 cases of twins without abortion were healthy.Conclusion:If there was no obvious abnormality either chromosome,CMA or ultrasound,and the isolated CCH with no fetal edema in the later stage had a good prognosis after birth.
引文
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[15] Sananes N,Guigue V,Kohler M,et al.Nuchal translucency and cystic hygroma colli in screening for fetal major congenital heart defects in a series of 12,910 euploid pregnancies[J].Ultrasound Obstet Gynecol,2010,35(3):273-279
[16] Kapoor S,Ghosh V,Dhua A,et al.Cystic hygroma and hirsutism in a child with Catel-Manzke syndrome[J].Clin Dysmorphol,2011.20(2):117-120
[17] Kang HJ,Liao AW,Brizot ML,et al.Prediction of intrauterine death and severe preterm delivery in twin pregnancies discordant for major fetal abnormality[J].Eur J Obstet Gynecol Reprod Biol,2014,175:115-118
[18] Best KE,Rankin J.Increased risk of congenital heart disease in twins in the North of England between 1998 and 2010[J].Heart,2015,101(22):1807-1812
[19] Choi SA,Ko JM,Shin CH,et al.Monozygotic twin discordant for Down syndrome:mos 47,XX,+21/46,XX and 46,XX[J].Eur J Pediatr,2013,172(8):1117-1120
[20] Dahoun S,Gagos S,Gagnebin M,et al.Monozygotic twins discordant for trisomy 21 and maternal 21q inheritance:a complex series of events[J].Am J Med Genet A,2008,146A(16):2086-2093
[21] 吴坚柱,周祎,林少宾,等.五例单绒毛膜双羊膜囊双胎核型不一致的产前诊断[J].中华医学遗传学杂志,2015,32(5):691-694
[2] Gedikbasi A,Gul A,Sargin A,et al.Cystic hygroma and lymphangioma:associated findings,perinatal outcome and prognostic factors in live-born infants[J].Arch Gynecol Obstet,2007,276(5):491-498
[3] Huang J,Leung TY,Choy KW.First-trimester cystic hygroma:relationship of nuchal translucency thickness and outcomes[J].Obstet Gynecol,2013,121(1):192
[4] Molina FS,Avgidou K,Kagan KO,et al.Cystic hygromas,nuchal edema,and nuchal translucency at 11-14 weeks of gestation[J].Obstet Gynecol,2006,107(3):678-683
[5] Greene N.First-trimester sonographic screening for Down syndrome[J].Obstet Gynecol,2004,103(5 Pt 1):1000;author reply 1001
[6] Ganapathy R,Guven M,Sethna F,et al.Natural history and outcome of prenatally diagnosed cystic hygroma[J].Prenat Diagn,2004,24(12):965-968
[7] Grande M,Jansen FA,Blumenfeld YJ,et al.Genomic microarray in fetuses with increased nuchal translucency and normal karyotype:a systematic review and meta-analysis[J].Ultrasound Obstet Gynecol,2015,46(6):650-658
[8] Hillman SC1,Pretlove S,Coomarasamy A,et al.Additional information from array comparative genomic hybridization technology over conventional karyotyping in prenatal diagnosis:a systematic review and meta-analysis[J].Ultrasound Obstet Gynecol,2011,37(1):6-14
[9] Huang J,Poon LC,Akolekar R,et al.Is high fetal nuchal translucency associated with submicroscopic chromosomal abnormalities on array CGH[J]? Ultrasound Obstet Gynecol,2014,43(6):620-624
[10] Gezdirici A,Ekiz A,Güle?倞 EY,et al.How necessary is to analyze PTPN11 gene in fetuses with first trimester cystic hygroma and normal karyotype[J]? J Matern Fetal Neonatal Med,2017,30(8):938-941
[11] Won HS,Yoo HK,Lee PR,et al.A case of achondrogenesis type II associated with huge cystic hygroma:prenatal diagnosis by ultrasonography[J].Ultrasound Obstet Gynecol,1999,14(4):288-290
[12] Scholl J,Durfee SM,Russell MA,et al.First-trimester cystic hygroma:relationship of nuchal translucency thickness and outcomes[J].Obstet Gynecol,2012,120(3):551-559
[13] Kharrat R1,Yamamoto M,Roume J,et al.Karyotype and outcome of fetuses diagnosed with cystic hygroma in the first trimester in relation to nuchal translucency thickness[J].Prenat Diagn,2006,26(4):369-372
[14] Tanriverdi HA,Ertan AK,Hendrik HJ,et al.Outcome of cystic hygroma in fetuses with normal karyotypes depends on associated findings[J].Eur J Obstet Gynecol Reprod Biol,2005,118(1):40-46
[15] Sananes N,Guigue V,Kohler M,et al.Nuchal translucency and cystic hygroma colli in screening for fetal major congenital heart defects in a series of 12,910 euploid pregnancies[J].Ultrasound Obstet Gynecol,2010,35(3):273-279
[16] Kapoor S,Ghosh V,Dhua A,et al.Cystic hygroma and hirsutism in a child with Catel-Manzke syndrome[J].Clin Dysmorphol,2011.20(2):117-120
[17] Kang HJ,Liao AW,Brizot ML,et al.Prediction of intrauterine death and severe preterm delivery in twin pregnancies discordant for major fetal abnormality[J].Eur J Obstet Gynecol Reprod Biol,2014,175:115-118
[18] Best KE,Rankin J.Increased risk of congenital heart disease in twins in the North of England between 1998 and 2010[J].Heart,2015,101(22):1807-1812
[19] Choi SA,Ko JM,Shin CH,et al.Monozygotic twin discordant for Down syndrome:mos 47,XX,+21/46,XX and 46,XX[J].Eur J Pediatr,2013,172(8):1117-1120
[20] Dahoun S,Gagos S,Gagnebin M,et al.Monozygotic twins discordant for trisomy 21 and maternal 21q inheritance:a complex series of events[J].Am J Med Genet A,2008,146A(16):2086-2093
[21] 吴坚柱,周祎,林少宾,等.五例单绒毛膜双羊膜囊双胎核型不一致的产前诊断[J].中华医学遗传学杂志,2015,32(5):691-694