Burrill Natalie, Schindewolf Erica, Pilchman Lisa, Wright Renee, Crane Haley, Gebb Juliana, Khalek Nahla, Soni Shelly, Paidas Teefey Christina, Oliver Edward R, Linn Rebecca, Moldenhauer Julie S
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Undiagnosed Disease Program, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Prenat Diagn. 2025 Mar;45(3):310-317. doi: 10.1002/pd.6735. Epub 2025 Jan 1.
To investigate the exome sequencing (ES) detection rate among fetuses with congenital anomalies and describe the rates in the setting of multiple versus isolated anomalies, perinatal autopsy, and family history of a previously affected child.
A single-center retrospective chart review was conducted on 397 anomalous fetuses that underwent ES from May 2012 through December 2023. Medical record review included demographics, imaging, and genetic testing.
The overall ES diagnostic rate was 34.3%. The rate of diagnosis was 31.6% in fetuses with a single anomaly and 42.6% in fetuses with 4 or more major organ systems involved. Of the fetuses with a single anomaly, lymphatic, craniofacial, skeletal, and neurological anomalies had the highest diagnostic rate on ES. 38.6% of deceased fetuses who underwent autopsy had a genetic diagnosis. Additionally, families who had a previously affected child had a 45.5% diagnostic rate.
ES is an important tool that should be offered in pregnancies affected with congenital abnormalities or at the time of fetal demise or termination. The diagnostic rate of ES in the prenatal setting is also highly dependent on comprehensive phenotyping. With diagnostic ES results, reproductive technology and testing options are available in subsequent pregnancies.
研究先天性异常胎儿的外显子组测序（ES）检测率，并描述在多发与单发异常、围产期尸检以及有患病儿童家族史情况下的检测率。
对2012年5月至2023年12月期间接受ES检测的397例异常胎儿进行单中心回顾性病历审查。病历审查包括人口统计学、影像学和基因检测。
ES总体诊断率为34.3%。单发异常胎儿的诊断率为31.6%，累及4个或更多主要器官系统的胎儿诊断率为42.6%。在单发异常胎儿中，淋巴、颅面、骨骼和神经异常的ES诊断率最高。接受尸检的死亡胎儿中有38.6%获得了基因诊断。此外，有患病儿童家族史的家庭诊断率为45.5%。
ES是一种重要工具，应在先天性异常妊娠、胎儿死亡或终止妊娠时提供。产前环境中ES的诊断率也高度依赖于全面的表型分析。有了ES诊断结果，后续妊娠可采用生殖技术和检测选项。
