Greenbaum Lior, Maya Idit, Sagi-Dain Lena, Sukenik-Halevy Rivka, Berkenstadt Michal, Yonath Hagith, Rienstein Shlomit, Shalata Adel, Katorza Eldad, Singer Amihood
The Danek Gertner Institute of Human Genetics (L.G., M.B., H.Y., S.R.), Sheba Medical Center, Tel Hashomer; The Joseph Sagol Neuroscience Center (L.G.), Sheba Medical Center, Tel Hashomer; Sackler Faculty of Medicine (L.G., I.M., R.S.-H., M.B., H.Y., E.K.), Tel Aviv University; Recanati Genetics Institute (I.M., R.S.-H.), Beilinson Hospital, Rabin Medical Center, Petach Tikva; Genetics Institute (L.S.-D.), Carmel Medical Center, Affiliated to the Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa; Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer; The Simon Winter Institute for Human Genetics (A.S.), Bnai Zion Medical Center, Haifa; Department of Obstetrics and Gynecology (E.K.), Sheba Medical Center, Tel Hashomer; and Department of Community Genetics (A.S.), Public Health Services, Ministry of Health, Jerusalem, Israel.
Neurol Genet. 2021 May 28;7(3):e585. doi: 10.1212/NXG.0000000000000585. eCollection 2021 Jun.
We investigated the detection rate of clinically significant chromosomal microarray analysis (CMA) results in pregnancies with sonographic diagnosis of fetal corpus callosum anomalies (CCA) or posterior fossa anomalies (PFA).
All CMA tests in pregnancies with CCA or PFA performed between January 2015 and June 2020 were retrospectively evaluated from the Israeli Ministry of Health database. The rate of CMA with clinically significant (pathogenic or likely pathogenic) findings was calculated and compared to a local Israeli cohort of 5,541 pregnancies with normal ultrasound.
One hundred eighty-two pregnancies were enrolled: 102 cases with CCA and 89 with PFA (9 cases had both). Clinically significant CMA results were found in 7/102 of CCA (6.9%) and in 7/89 of PFA (7.9%) cases. The CMA detection rate in pregnancies with isolated CCA (2/57, 3.5%) or PFA (2/50, 4.0%) was lower than in nonisolated cases, including additional CNS and/or extra-CNS sonographic anomalies (CCA-5/45, 11.1%; PFA-5/39, 12.8%), but this was not statistically significant. However, the rate among pregnancies that had extra-CNS anomalies, with or without additional CNS involvement (CCA-5/24, 20.8%; PFA-5/29, 17.2%), was significantly higher compared to all other cases ( = 0.0075 for CCA; = 0.035 for PFA). Risk of CMA with clinically significant results for all and nonisolated CCA or PFA pregnancies was higher compared to the background risk reported in the control cohort ( < 0.001), but was not significant for isolated cases.
Our findings suggest that CMA testing is beneficial for the genetic workup of pregnancies with CCA or PFA, and is probably most informative when additional extra-CNS anomalies are observed.
我们调查了超声诊断为胎儿胼胝体异常（CCA）或后颅窝异常（PFA）的妊娠中，临床显著染色体微阵列分析（CMA）结果的检出率。
从以色列卫生部数据库中回顾性评估2015年1月至2020年6月期间对患有CCA或PFA的妊娠进行的所有CMA检测。计算具有临床显著（致病或可能致病）结果的CMA发生率，并与以色列当地一组5541例超声检查正常的妊娠进行比较。
共纳入182例妊娠：102例CCA和89例PFA（9例同时患有两者）。在CCA病例中，7/102（6.9%）发现临床显著的CMA结果；在PFA病例中，7/89（7.9%）发现临床显著的CMA结果。孤立性CCA（2/57，3.5%）或PFA（2/50，4.0%）妊娠的CMA检出率低于非孤立性病例，包括额外的中枢神经系统和/或中枢神经系统外超声异常（CCA-5/45，11.1%；PFA-5/39，12.8%），但差异无统计学意义。然而，无论有无额外中枢神经系统受累，患有中枢神经系统外异常的妊娠中的发生率（CCA-5/24，20.8%；PFA-5/29，17.2%）与所有其他病例相比显著更高（CCA为0.0075；PFA为0.035）。所有以及非孤立性CCA或PFA妊娠中具有临床显著结果的CMA风险高于对照队列中报告的背景风险（<0.001），但孤立性病例无显著差异。
我们的研究结果表明，CMA检测对于患有CCA或PFA的妊娠的基因检查有益，并且当观察到额外的中枢神经系统外异常时可能最具信息价值。
