目的:Wolf-Hirschhorn综合征(WHS)是一种先天性畸形综合征,预后较差。它与染色体4p16.3的杂合缺失有关。足够的产前表型知识和适当的产前咨询对于宫内诊断至关重要。
方法:回顾性分析2017年5月至2022年9月在我院进行低深度全基因组测序(拷贝数变异测序)诊断的11例产前WHS病例,并详细回顾其产前超声报告。我们还分析了WHS病例(包括产前和产后)在过去20年发表的文献中异常的产前超声检查结果。
结果:在我院产前诊断为WHS的11例胎儿中,四例产前超声检查异常,包括缩小的肾脏,室间隔缺损,一个小肚子,胎儿生长受限(FGR),后颅窝增大,和柔软的超声波标记。我们的4例病例与114例其他医疗机构发表的产前超声异常的WHS病例相结合。在118个案例中,59.3%(118个中的70个)是多发性畸形。在所有118例中观察到的最常见的超声特征是FGR(76.3%,90of118),其次是面部异常(28.8%,34of118),中枢神经系统异常(27.1%,32of118),和软超声标记(23.7%,28of118)。其他不太常见的表型包括心脏异常(19.5%,23of118)泌尿生殖系统异常(19.5%,23of118)NT/NF增加(12.7%,118的15个)骨骼异常(11.9%,118的14个)单脐动脉(10.2%,118的12)胃肠道异常(9.3%,118的11个)羊水过少(8.5%,118的10个)囊性水瘤(5.1%,118个中的六个),积液/胸腔积液/腹水(2.5%,三个118),和羊水过多(2.5%,118个中的三个)。
结论:本研究通过分析产前超声异常,提高了我们对WHS产前表现的理解。产前超声异常的及时识别可以为孕妇提供准确的咨询,改善WHS的产前检测,并实现早期产前管理和WHS干预。
Wolf-Hirschhorn syndrome (WHS) is a congenital malformation syndrome with poor prognosis. It is associated with a heterozygous deletion of chromosome 4p16.3. Adequate knowledge of prenatal phenotypes and proper prenatal counseling are essential for intrauterine diagnosis.
We retrospectively analyzed 11 prenatal cases of WHS diagnosed using low-depth whole-genome sequencing (copy number variation sequencing) performed at our hospital from May 2017 to September 2022 and reviewed their prenatal ultrasound reports in detail. We also analyzed WHS cases (including prenatal and postnatal) with abnormal prenatal ultrasound findings in the published literature over the past 20 years.
Among the 11 fetuses with a prenatal diagnosis of WHS in our hospital, four cases showed abnormal prenatal ultrasound findings, including shrunken kidneys, ventricular septal defect, a small stomach, fetal growth restriction (FGR), enlarged posterior fossa, and soft ultrasonic markers. Our four cases were combined with 114 published WHS cases with prenatal ultrasound abnormalities from other medical institutions. Of the 118 cases, 59.3% (70 of 118) were multiple malformations. The most frequent ultrasound features observed in all 118 cases were FGR (76.3%, 90 of 118), followed by facial anomalies (28.8%, 34 of 118), central nervous system anomalies (27.1%, 32 of 118), and soft ultrasound markers (23.7%, 28 of 118). Other less common phenotypes included cardiac anomalies (19.5%, 23 of 118), genitourinary anomalies (19.5%, 23 of 118), increased NT/NF (12.7%, 15 of 118), skeletal anomalies (11.9%, 14 of 118), a single umbilical artery (10.2%, 12 of 118), gastrointestinal anomalies (9.3%, 11 of 118), oligohydramnios (8.5%, 10 of 118), cystic hygroma (5.1%, six of 118), hydrops/pleural effusion/ascites (2.5%, three of 118), and polyhydramnios (2.5%, three of 118).
This study improved our understanding of the prenatal presentation of WHS by analyzing prenatal ultrasound abnormalities. The timely identification of prenatal ultrasound abnormalities can provide accurate consultation for pregnant women, improve the prenatal detection of WHS, and enable early prenatal management and intervention of WHS.