Wolf-Hirschhorn综合征2例胎儿的产前诊断及遗传学分析

Prenatal diagnosis and genetic analysis of two fetuses with Wolf-Hirschhorn syndrome

目的探讨2例Wolf-Hirschhorn综合征(WHS)胎儿的产前超声特点及遗传学病因。方法回顾性分析2017年7月至2019年8月在清远市人民医院产前诊断中心超声筛查提示为WHS的2例胎儿的超声影像学资料。通过羊水染色体核型分析以及染色体微阵列分析(CMA)对胎儿进行产前诊断。本研究通过清远市人民医院医学伦理委员会的审查(伦理号:IRB-2022-064)。结果2例胎儿产前超声诊断均提示存在宫内生长受限(IUGR)、颅面异常、心血管异常等WHS相关表型。2例胎儿羊水核型分析均为隐匿性易位导致4号染色体短臂部分缺失,家系分析提示胎儿1为新发变异,胎儿2为父源性。CMA检测提示胎儿1染色体4p16.3p16.1区存在约8.7 Mb的缺失片段,8p23.3p23.1区存在约6.8 Mb的重复片段,胎儿2染色体4p16.3p15.31区存在约20.05 Mb的缺失片段,9p24.3p24.1区存在约7.66 Mb的重复片段。胎儿1的染色体核型被确定为46,XN,der(4)t(4;8)(p16.1;p23.1)dn.arr[hg19]4p16.3p16.1(68345_8721580)×1,8p23.3p23.1(158048_6933745)×3;胎儿2为46,XN,der(4)t(4;9)(p15.3;p24)dpat.arr[hg19]4p16.3p15.31(68345_20116061)×1,9p24.3p24.1(208454_7868292)×3。结论4号染色体短臂末端缺失是导致胎儿WHS表型的主要原因。产前超声发现胎儿IUGR、肾脏异常、颅面部和心血管等多种异常时,需高度警惕WHS。

ObjectiveTo explore the prenatal ultrasound phenotype and genetic basis of two fetuses with Wolf-Hirschhorn syndrome(WHS).MethodsA retrospective analysis was conducted on the ultrasound imaging data of two fetuses suspected for WHS at the Prenatal Diagnostic Center of Qingyuan People′s Hospital in July 2017 and August 2019,respectively.Amniotic fluid samples of the two fetuses were subjected to chromosomal karyotyping and chromosomal microarray analysis(CMA).This study was approved by Medical Ethics Committee of the Qingyuan People′s Hospital(Ethics No.IRB-2022-064).ResultsPrenatal ultrasound examination of the two fetuses had consistently revealed WHS-associated traits including intrauterine growth restriction(IUGR),craniofacial abnormalities and cardiovascular anomalies.Karyotyping analysis suggested that both fetuses had harbored cryptic chromosomal translocations involving partial deletion of 4p.And parental verification revealed that it was de novo for fetus 1 and paternal for fetus 2.CMA has confirmed that fetus 1 had an approximately 8.7 Mb deletion at 4p16.3p16.1 and a 6.8 Mb duplication at 8p23.1p23.1,whilst fetus 2 had a 20.05 Mb deletion at 4p16.3p15.31 and a 7.66 Mb duplication at 9p24.3p24.1.The karyotype of fetus 1 was determined as 46,XN,der(4)t(4;8)(p16.1;p23.1)dn.arr[hg19]4p16.3p16.1(68345_8721580)×1,8p23.3p23.1(158048_6933745)×3,and that of fetus 2 was determined as 46,XN,der(4)t(4;9)(p15.3;p24)dpat.arr[hg19]4p16.3p15.31(68345_20116061)×1,9p24.3p24.1(208454_7868292)×3.ConclusionThe 4p deletion is probably the main cause for the WHS phenotype in both fetuses.WHS should be suspected when IUGR,renal anomalies,craniofacial and cardiovascular abnormalities are detected upon prenatal ultrasound screening.