The yield of chromosomal microarray testing for cases of abnormal fetal head circumference

Yael Pasternakhttp://orcid.org/https://orcid.org/0000-0003-4292-8133 1 , 2 , Amihood Singer 3 , Idit Maya 2 , 4 , Lena Sagi-Dain 5 , Shay Ben-Shachar 2 , 6 , Morad Khayat 7 , Lior Greenbaum 8 , Michal Feingold-Zadok 9 , Sharon Zeligson 10  and Rivka Sukenik Halevy 2 , 4
  • 1 Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel
  • 2 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • 3 Community Genetics, Public Health Services, Ministry of Health, Jerusalem, Israel
  • 4 Recanati Genetic Institute, Rabin Medical Center, Petah Tikva, Israel
  • 5 Genetics Institute, Carmel Medical Center, affiliated to the Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
  • 6 Genetics Institute, Sorasky Medical Center, Tel Aviv, Israel
  • 7 Institute of Human Genetics, Haemek Medical Center, Afula, Israel
  • 8 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel; and The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel
  • 9 Genetics Institute, Shamir Medical Center, Zerifin, Israel
  • 10 Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel
Yael PasternakORCID iD: https://orcid.org/0000-0003-4292-8133, Amihood Singer, Idit Maya
  • Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Recanati Genetic Institute, Rabin Medical Center, Petah Tikva, Israel
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, Lena Sagi-Dain
  • Genetics Institute, Carmel Medical Center, affiliated to the Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
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, Shay Ben-Shachar
  • Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Genetics Institute, Sorasky Medical Center, Tel Aviv, Israel
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, Morad Khayat, Lior Greenbaum
  • Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel; and The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel
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, Michal Feingold-Zadok, Sharon Zeligson and Rivka Sukenik Halevy
  • Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Recanati Genetic Institute, Rabin Medical Center, Petah Tikva, Israel
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  • degruyter.comGoogle Scholar

Abstract

Objectives

Chromosomal microarray analysis (CMA) is the method of choice for genetic work-up in cases of fetal malformations. We assessed the detection rate of CMA in cases of abnormal fetal head circumference (HC).

Methods

The study cohort was based on 81 cases of amniocenteses performed throughout Israel for the indication of microcephaly (53) or macrocephaly (28), from January 2015 through December 2018. We retrieved data regarding the clinical background, parental HCs and work-up during the pregnancy from genetic counseling summaries and from patients’ medical records.

Results

There was only one likely pathogenic CMA result (1.89%): a 400-kb microdeletion at 16p13.3 detected in a case of isolated microcephaly. No pathogenic results were found in the macrocephaly group. Most fetuses with microcephaly were female (87.8%), while the majority with macrocephaly were males (86.4%).

Conclusions

The results imply that CMA analysis in pregnancies with microcephaly may carry a small yield compared to other indications. Regarding macrocephaly, our cohort was too small to draw conclusions. In light of the significant gender effect on the diagnosis of abnormal HC, standardization of fetal HC charts according to fetal gender may normalize cases that were categorized outside the normal range and may increase the yield of CMA for cases of abnormal HC.

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