Prenatal microarray analysis in right aortic arch—a retrospective cohort study and review of the literature



To examine the risk for clinically significant chromosomal microarray analysis (CMA) findings in fetal right aortic arch (RAA).


Data from all CMA analyses performed owing to isolated RAA reported to the Israeli Ministry of Health between January 2013 and September 2016 were evaluated retrospectively. Risk for abnormal CMA findings was compared with two control populations, based on both previously described 9272 pregnancies with normal ultrasound, and on a local cohort of 5541 pregnancies undergoing CMA testing owing to maternal request. In addition, Pubmed database search was conducted for original researches examining this issue.


Of 94 CMA analyses performed owing to isolated RAA, six (6.4%) pathogenic findings were detected (47,XX + 21; 45,X; two 22q11.2 microdeletions; 10p15.3 microdeletion and 16p11.2 duplication). Compared with control groups, an isolated RAA yielded a significantly increased relative risk for abnormal CMA results. Literature search yielded two additional retrospective studies describing microarray testing in RAA and encompassing 57 cases. The overall risk for clinically significant CMA findings was 6.62% (10/151).


CMA testing is indicated in cases of prenatal isolated RAA, even in the era of advanced sonographic equipment, routine biochemical screening for Down syndrome and available non-invasive prenatal testing.

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  1. 1.

    Achiron R, Rotstein Z, Heggesh J, Bronshtein M, Zimand S, Lipitz S, et al. Anomalies of the fetal aortic arch: a novel sonographic approach to in-utero diagnosis. Ultrasound Obstet Gynecol. 2002;20:553–557.

    CAS  Article  Google Scholar 

  2. 2.

    Hanneman K, Newman B, Chan F. Congenital variants and anomalies of the aortic arch. Radiographics. 2017;37:32–51.

    Article  Google Scholar 

  3. 3.

    McElhinney DB, Clark BJ 3rd, Weinberg PM, Kenton ML, McDonald-McGinn D, Driscoll DA, et al. Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching. J Am Coll Cardiol. 2001;37:2114–2119.

    CAS  Article  Google Scholar 

  4. 4.

    D’Antonio F, Khalil A, Zidere V, Carvalho JS. Fetuses with right aortic arch: a multicenter cohort study and meta-analysis. Ultrasound Obstet Gynecol. 2016;47:423–432.

    Article  Google Scholar 

  5. 5.

    American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal–Fetal Medicine. Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders. Obstet Gynecol. 2016;127:e128–e122..

  6. 6.

    Peng R, Xie HN, Zheng J, Zhou Y, Lin MF. Fetal right aortic arch: associated anomalies, genetic anomalies with chromosomal microarray analysis and postnatal outcome. Prenat Diagn. 2017;37:329–335.

    CAS  Article  Google Scholar 

  7. 7.

    O’Mahony EF, Hutchinson DP, McGillivray G, Nisbet DL, Palma-Dias R. Right-sided aortic arch in the age of microarray. Prenat Diagn. 2017;37:440–445.

    Article  Google Scholar 

  8. 8.

    Maya I, Kahana S, Yeshaya J, Tenne T, Yacobson S, Agmon-Fishman I, et al. Chromosomal microarray analysis in fetuses with aberrant right subclavian artery. Ultrasound Obstet Gynecol. 2016;49:337–341.

    Article  Google Scholar 

  9. 9.

    Svirsky R, Reches A, Brabbing-Goldstein D, Bar-Shira A, Yaron Y. Association of aberrant right subclavian artery with abnormal karyotype and microarray results. Prenat Diagn. 2017;37:808–811.

    CAS  Article  Google Scholar 

  10. 10.

    Maya I, Sharony R, Yacobson S, Kahana S, Yeshaya J, Tenne T, et al. When genotype is not predictive of phenotype: implications for genetic counseling based on 21,594 chromosomal microarray analysis examinations. Genet Med. 2017;20:128–131.

    Article  Google Scholar 

  11. 11.

    Fiorentino F, Caiazzo F, Napolitano S, Spizzichino L, Bono S, Sessa M, et al. Introducing array comparative genomic hybridization into routine prenatal diagnosis practice: a prospective study on over 1000 consecutive clinical cases. Prenat Diagn. 2011;31:1270–1282.

    Article  Google Scholar 

  12. 12.

    Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST, Working Group of the American College of Medical Genetics Laboratory Quality Assurance C. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011;13:680–685.

    Article  Google Scholar 

  13. 13.

    Callaway JL, Shaffer LG, Chitty LS, Rosenfeld JA, Crolla JA. The clinical utility of microarray technologies applied to prenatal cytogenetics in the presence of a normal conventional karyotype: a review of the literature. Prenat Diagn. 2013;33:1119–1123.

    Article  Google Scholar 

  14. 14.

    Coe BP, Witherspoon K, Rosenfeld JA, van Bon BW, Vulto-van Silfhout AT, Bosco P, et al. Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nat Genet. 2014;46:1063–1071.

    CAS  Article  Google Scholar 

  15. 15.

    DeScipio C, Conlin L, Rosenfeld J, Tepperberg J, Pasion R, Patel A, et al. Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization. Am J Med Genet A. 2012;158A:2152–2161.

    Article  Google Scholar 

  16. 16.

    Vargiami E, Ververi A, Kyriazi M, Papathanasiou E, Gioula G, Gerou S, et al. Severe clinical presentation in monozygotic twins with 10p15.3 microdeletion syndrome. Am J Med Genet A. 2014;164A:764–768.

    Article  Google Scholar 

  17. 17.

    Eggert M, Muller S, Heinrich U, Mehraein Y. A new familial case of microdeletion syndrome 10p15.3. Eur J Med Genet. 2016;59:179–182.

    Article  Google Scholar 

  18. 18.

    Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P, Itsara A, et al. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet. 2010;42:203–209.

    CAS  Article  Google Scholar 

  19. 19.

    D’Angelo D, Lebon S, Chen Q, Martin-Brevet S, Snyder LG, Hippolyte L, et al. Defining the effect of the 16p11.2 duplication on cognition, behavior, and medical comorbidities. JAMA Psychiatry. 2016;73:20–30.

    Article  Google Scholar 

  20. 20.

    Chang H, Li L, Li M, Xiao X. Rare and common variants at 16p11.2 are associated with schizophrenia. Schizophr Res. 2016;184:105–108.

    Article  Google Scholar 

  21. 21.

    Maillard AM, Ruef A, Pizzagalli F, Migliavacca E, Hippolyte L, Adaszewski S, et al. The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity. Mol Psychiatry. 2015;20:140–147.

    CAS  Article  Google Scholar 

  22. 22.

    Shinawi M, Liu P, Kang SH, Shen J, Belmont JW, Scott DA, et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 2010;47:332–341.

    CAS  Article  Google Scholar 

  23. 23.

    Schaaf CP, Goin-Kochel RP, Nowell KP, Hunter JV, Aleck KA, Cox S, et al. Expanding the clinical spectrum of the 16p11.2 chromosomal rearrangements: three patients with syringomyelia. Eur J Human Genet. 2011;19:152–156.

    Article  Google Scholar 

  24. 24.

    Lazier J, Fruitman D, Lauzon J, Bernier F, Argiropoulos B, Chernos J, et al. Prenatal array comparative genomic hybridization in fetuses with structural cardiac anomalies. J Obstet Gynaecol Can. 2016;38:619–626.

    Article  Google Scholar 

  25. 25.

    McDonald-McGinn DM, Kirschner R, Goldmuntz E, Sullivan K, Eicher P, Gerdes M, et al. ThePhiladelphia story: the 22q11.2 deletion: report on 250 patients. Genet Couns. 1999;10:11–24.

    CAS  PubMed  Google Scholar 

  26. 26.

    Bassuk AG, Muthuswamy LB, Boland R, Smith TL, Hulstrand AM, Northrup H, et al. Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene. Hum Mol Genet. 2013;22:1097–111.

    CAS  Article  Google Scholar 

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We are thankful to all the genetic counselors and laboratory personnel who made this data acquisition possible.

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Correspondence to Lena Sagi-Dain.

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Maya, I., Singer, A., Baris, H. et al. Prenatal microarray analysis in right aortic arch—a retrospective cohort study and review of the literature. J Perinatol 38, 468–473 (2018).

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