Accessible Unlicensed Requires Authentication Published by De Gruyter April 28, 2020

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

Yael Pasternak ORCID logo, Amihood Singer, Idit Maya, Lena Sagi-Dain, Shay Ben-Shachar, Morad Khayat, Lior Greenbaum, Michal Feingold-Zadok, Sharon Zeligson and Rivka Sukenik Halevy

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.


Corresponding author: Yael Pasternak, Yael Pasternak, Department of Obstetrics and Gynecology, Meir Medical Center, 59 Tchernichovsky St., Kfar Saba, Israel; and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, Phone: +972-97472232, Fax: +972-9-7472465

  1. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  2. Research funding: None declared.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was approved by the Helsinki Ethics Committee – approval no. MOH2016.

References

1. Chervenak FA, Jeanty P, Cantraine F, Chitkara U, Venus I, Berkowitz RL, et al. The diagnosis of fetal microcephaly. Am J Obstet Gynecol 1984;149:512–7.Search in Google Scholar

2. Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating fetal age: computer-assisted analysis of multiple fetal growth parameters. Radiology 1984;152:497–501.Search in Google Scholar

3. Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB. A developmental and genetic classification for malformations of cortical development: update 2012. Brain 2012;135(Pt 5):1348–69.Search in Google Scholar

4. Krauss MJ, Morrissey AE, Winn HN, Amon E, Leet TL. Microcephaly: an epidemiologic analysis. Am J Obstet Gynecol 2003;188:1484–9; discussion 9–90.Search in Google Scholar

5. Ashwal S, Michelson D, Plawner L, Dobyns WB. Practice parameter: evaluation of the child with microcephaly (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2009;73:887–97.Search in Google Scholar

6. Alcantara D, O’Driscoll M. Congenital microcephaly. Am J Med Genet C Semin Med Genet 2014;166c:124–39.Search in Google Scholar

7. Opitz JM, Holt MC. Microcephaly: general considerations and aids to nosology. J Craniofac Genet Dev Biol 1990;10:175–204.Search in Google Scholar

8. von der Hagen M, Pivarcsi M, Liebe J, von Bernuth H, Didonato N, Hennermann JB, et al. Diagnostic approach to microcephaly in childhood: a two-center study and review of the literature. Dev Med Child Neurol 2014;56:732–41.Search in Google Scholar

9. Boonsawat P, Joset P, Steindl K, Oneda B, Gogoll L, Azzarello-Burri S, et al. Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly. Genet Med 2019;21:2043–58.Search in Google Scholar

10. Dahlgren L, Wilson RD. Prenatally diagnosed microcephaly: a review of etiologies. Fetal Diagn Ther 2001;16:323–6.Search in Google Scholar

11. Ji X, Pan Q, Wang Y, Wu Y, Zhou J, Liu A, et al. Prenatal diagnosis of recurrent distal 1q21.1 duplication in three fetuses with ultrasound anomalies. Front Genet 2018;9:275.Search in Google Scholar

12. Herriges JC, Brown S, Longhurst M, Ozmore J, Moeschler JB, Janze A, et al. Identification of two 14q32 deletions involving DICER1 associated with the development of DICER1-related tumors. Eur J Med Genet 2019;62:9–14.Search in Google Scholar

13. Shaheen R, Maddirevula S, Ewida N, Alsahli S, Abdel-Salam GMH, Zaki MS, et al. Genomic and phenotypic delineation of congenital microcephaly. Genet Med 2019;21:545–52.Search in Google Scholar

14. Foster A, Zachariou A, Loveday C, Ashraf T, Blair E, Clayton-Smith J, et al. The phenotype of Sotos syndrome in adulthood: a review of 44 individuals. Am J Med Genet C Semin Med Genet 2019;181:502–8.Search in Google Scholar

15. Plamper M, Gohlke B, Schreiner F, Woelfle J. Phenotype-driven diagnostic of PTEN hamartoma tumor syndrome: macrocephaly, but neither height nor weight development, is the important trait in children. Cancers (Basel) 2019;11:E975.Search in Google Scholar

16. Practice bulletin No. 162: prenatal diagnostic testing for genetic disorders. Obstet Gynecol 2016;127:e108–22.Search in Google Scholar

17. Shaffer LG, Rosenfeld JA, Dabell MP, Coppinger J, Bandholz AM, Ellison JW, et al. Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound. Prenat Diagn 2012;32:986–95.Search in Google Scholar

18. Raun N, Mailo J, Spinelli E, He X, McAvena S, Brand L, et al. Quantitative phenotypic and network analysis of 1q44 microdeletion for microcephaly. Am J Med Genet A 2017;173:972–7.Search in Google Scholar

19. Nevado J, Rosenfeld JA, Mena R, Palomares-Bralo M, Vallespin E, Angeles Mori M, et al. PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome. Eur J Hum Genet 2015;23:1615–26.Search in Google Scholar

20. Wang HD, Liu L, Wu D, Li T, Cui CY, Zhang LZ, et al. Clinical and molecular cytogenetic analyses of four families with 1q21.1 microdeletion or microduplication. J Gene Med 2017;19:e2948.Search in Google Scholar

21. Sagi-Dain L, Cohen Vig L, Kahana S, Yacobson S, Tenne T, Agmon-Fishman I, et al. Chromosomal microarray vs. NIPS: analysis of 5541 low-risk pregnancies. Genet Med 2019;21:2462–7.Search in Google Scholar

22. Srebniak MI, Joosten M, Knapen M, Arends LR, Polak M, van Veen S, et al. Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal aberrations: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018;51:445–52.Search in Google Scholar

23. Hook EB. Rates of chromosome abnormalities at different maternal ages. Obstet Gynecol 1981;58:282–5.Search in Google Scholar

24. South ST, Lee C, Lamb AN, Higgins AW, Kearney HM, Working Group for the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee. ACMG standards and guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med 2013;15:901–9.Search in Google Scholar

25. Nellhaus G. Head circumference from birth to eighteen years. Practical composite international and interracial graphs. Pediatrics 1968;41:106–14.Search in Google Scholar

26. Lal D, Pernhorst K, Klein KM, Reif P, Tozzi R, Toliat MR, et al. Extending the phenotypic spectrum of RBFOX1 deletions: sporadic focal epilepsy. Epilepsia 2015;56:e129–33.Search in Google Scholar

27. Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol 2013;170:1–7.Search in Google Scholar

28. Malinger G, Lev D, Ben-Sira L, Hoffmann C, Herrera M, Vinals F, et al. Can syndromic macrocephaly be diagnosed in utero? Ultrasound Obstet Gynecol 2011;37:72–81.Search in Google Scholar

29. Melamed N, Meizner I, Mashiach R, Wiznitzer A, Glezerman M, Yogev Y. Fetal sex and intrauterine growth patterns. J Ultrasound Med 2013;32:35–43.Search in Google Scholar

30. Schwarzler P, Bland JM, Holden D, Campbell S, Ville Y. Sex-specific antenatal reference growth charts for uncomplicated singleton pregnancies at 15–40 weeks of gestation. Ultrasound Obstet Gynecol 2004;23:23–9.Search in Google Scholar

31. Galjaard S, Ameye L, Lees CC, Pexsters A, Bourne T, Timmerman D, et al. Sex differences in fetal growth and immediate birth outcomes in a low-risk Caucasian population. Biol Sex Differ 2019;10:48.Search in Google Scholar

Received: 2020-02-09
Accepted: 2020-04-06
Published Online: 2020-04-28
Published in Print: 2020-07-28

©2020 Walter de Gruyter GmbH, Berlin/Boston