Division of Perinatology, Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Arch Gynecol Obstet. 2022 Feb;305(2):323-342. doi: 10.1007/s00404-021-06125-4. Epub 2021 Jun 18.
We aimed to present the fetal ultrasound, cytogenetic/molecular testing and postmortem or postnatal clinical findings of cases with 22q11.2DS diagnosed prenatally.
A retrospective medical record review of 48 prenatal cases diagnosed with 22q11.2DS were evaluated in our institution. Detailed ultrasound examination was performed on all fetuses. Postmortem and postnatal examinations were evaluated. The microdeletions were detected by karyotyping or microarray, then confirmed by FISH. Descriptive statistical analysis was performed.
Demographic data of 48 prenatal cases including 46 singletons and 1 dichorionic diamniotic twin pregnancy were evaluated. The most common extracardiac anomaly was skeletal system anomalies (25%), in which PEV was the most frequent one (20.8%). Polyhydramnios rate was detected as 31%, in 6.6% as an isolated finding. Microdeletion has been detected by karyotyping in 13 cases (13/47, 27.7%) (including 2 unbalanced translocations), by FISH in 28 cases (28/48, 58.3%), by microarray/a-CGH testing in 7 cases. Microarray analysis showed that in one case with unbalanced translocation had two consecutive deletions; one was proximal and other one distal to critical region and not encompassing TBX1 gene but CRKL and LZTR1 genes.
The current study demonstrates the whole spectrum of atypical phenotypic and genotypic variations of 22q11.2DS in the largest prenatal case series reported to date. Therefore, differential diagnosis should be considered not solely in CHD, but also in the presence of isolated clubfeet and polyhydramnios. Establishing the diagnosis in the prenatal period may allow a postnatal multidisciplinary approach, as well as affect the actual prevalence of the disease.
本研究旨在介绍产前诊断为 22q11.2 微缺失综合征（22q11.2DS）的病例的胎儿超声、细胞遗传/分子检测及产后临床发现。
我们对本机构中 48 例产前诊断为 22q11.2DS 的病例进行了回顾性病历审查。所有胎儿均进行详细的超声检查。评估了尸检和产后检查结果。通过核型分析或微阵列检测到微缺失，然后通过 FISH 确认。采用描述性统计分析。
评估了 48 例产前病例的人口统计学数据，包括 46 例单胎妊娠和 1 例双绒毛膜双羊膜囊双胎妊娠。最常见的心脏外异常是骨骼系统异常（25%），其中 PEV 最常见（20.8%）。羊水过多的发生率为 31%，6.6%为孤立性发现。通过核型分析在 13 例（13/47，27.7%）（包括 2 例不平衡易位）中检测到微缺失，通过 FISH 在 28 例（28/48，58.3%）中，通过微阵列/a-CGH 检测在 7 例中检测到微缺失。微阵列分析显示，在 1 例不平衡易位中，有两个连续的缺失；一个位于近端，另一个位于远端临界区，不包括 TBX1 基因，但包括 CRKL 和 LZTR1 基因。
本研究展示了迄今为止报道的最大产前病例系列中 22q11.2DS 的非典型表型和基因型变异的全貌。因此，不仅应在 CHD 中考虑鉴别诊断，而且在孤立性马蹄内翻足和羊水过多的情况下也应考虑。在产前诊断可以允许产后多学科方法，也可以影响疾病的实际患病率。
