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Case Reports
. 2019 Nov;7(11):e00895.
doi: 10.1002/mgg3.895. Epub 2019 Sep 7.

Mosaic complete tetrasomy 21 in a fetus with complete atrioventricular septal defect and minor morphological variations

Vincent Gatinois  1 , Nicole Bigi  2 , Eve Mousty  3 , Jean Chiesa  4 , Yuri Musizzano  5 , Anouck Schneider  1 , Geneviève Lefort  1 , Lucile Pinson  2 , Jean-Baptiste Gaillard  1   4 , Clémence Ragon  6 , Marie-Josée Perez  2 , Magali Tournaire  1 , Patricia Blanchet  2 , Carole Corsini  2 , Emmanuelle Haquet  2 , Patrick Callier  6 , David Geneviève  2 , Franck Pellestor  1 , Jacques Puechberty  2
Affiliations
Case Reports

Mosaic complete tetrasomy 21 in a fetus with complete atrioventricular septal defect and minor morphological variations

Vincent Gatinois et al. Mol Genet Genomic Med. 2019 Nov.

Abstract

Background: Tetrasomy 21 is a very rare aneuploidy which could clinically resemble a Down syndrome. It was most often described in its partial form than complete. We report the prenatal, pathological and genetic characteristics of a fetus with mosaic complete tetrasomy 21. This is the second well-documented description of a complete tetrasomy 21 in the literature.

Methods: Prenatal and fetal pathological examinations, cytogenetic and molecular analyses were performed to characterize fetal features with tetrasomy 21.

Results: Prenatal ultrasound examination revealed an isolated complete atrioventricular septal defect with normal karyotype on amniotic fluid. After termination of pregnancy, clinical examination of the fetus evoked trisomy 21 or Down syndrome. Chromosomal microarray analysis and FISH on lung tissue showed a mosaicism with four copies of chromosome 21 (tetrasomy 21).

Conclusion: Our observation and the review of the literature reported the possibility of very weak mosaicism and disease-causing confined tissue-specific mosaicism in fetus or alive patients with chromosome 21 aneuploidy, mainly Down syndrome. In case of clinical diagnosis suggestive of Down syndrome, attention must be paid to the risk of false-negative test due to chromosomal mosaicism (very weak percentage, different tissue distribution). To overcome this risk, it is necessary to privilege the diagnostic techniques without culture step and to increase the number of cells and tissues analyzed, if possible. This study highlights the limits of microarray as the unique diagnostic approach in case of weak mosaic and French cytogenetics guidelines recommend to check anomalies seen in microarray by another technique on the same tissue.

Keywords: Down syndrome; Mosaicism; atrioventricular septal defect; prenatal diagnosis; tetrasomy 21; trisomy 21.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Results of FISH analysis. Left: Two pictures showing specific FISH probes for 13q14.2 locus (signals marked by white triangles) and 21q22.13 locus (signals marked by white arrows) hybridized on lung tissue. DAPI for counterstaining. Mosaicism of tetrasomic cells (four signals for the four copies of chromosome 21 and two signals for two copies of chromosome 13) and disomic cells for chromosome 21 (and chromosome 13). Right: Table showing cell counts for each FISH pattern on fetal tissues and amniotic fluid. Confirmation of mosaic tetrasomy 21 in lung tissue (74.5%) and uncultured amniotic fluid (13.7%) by FISH analysis with a percentage of trisomic 21 cells at the limit of the significance level
Figure 2
Figure 2
Fetal metaphasis and karyotype on amniotic fluid. Metaphasis (a) and Karyotype (b) with 48 chromosomes (R‐banding) and four free copies of chromosomes 21 (black asterisks), in favor of a free tetrasomy 21
See this image and copyright information in PMC

References

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