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

Abstract

BackgroundTetrasomy 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.MethodsPrenatal and fetal pathological examinations, cytogenetic and molecular analyses were performed to characterize fetal features with tetrasomy 21.ResultsPrenatal 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).ConclusionOur 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.

The first post‐natal clinical description of true mosaic complete tetrasomy 21: A case report

“…This case was later argued to be a misdiagnosis, since leukemia is known to cause multiple copies of chromosome 21 in affected red blood cells. Another case of complete mosaic tetrasomy 21 also resulted in clinical observation; however, it was of the aborted fetus at 30 weeks gestation and not of a neonate (Gatinois et al, 2019). To our knowledge, this is the first postnatal clinical description of true complete mosaic tetrasomy 21 case.…”

“…Eight of these cases were partial tetrasomy and six were complete tetrasomy. Previous reported cases of partial trisomy were the result of an isodicentric chromosome within the proximal portion of the q arm of chromosome 21, not the distal region known for producing the typical Down syndrome phenotype (Gatinois et al, 2019). As a result, these cases of partial tetrasomy 21 tend to show only a few signs common to trisomy 21 with several other nonspecific abnormalities.…”

“…Complete tetrasomy, in contrast, is thought to be caused by two incidences of non‐disjunction, either subsequently in maternal Meiosis I/II (Liehr et al, 2001) or concurrently in paternal and maternal Meiosis (Gatinois et al, 2019). Although six cases have been reported, the clinical features of true complete mosaic tetrasomy have never been documented in a postnatal case (Gatinois et al, 2019). Here we present a patient with complete mosaic tetrasomy 21 that presents a unique opportunity to understand the clinical phenotype of this rare chromosome aneuploidy.…”