Trisomy 16 and trisomy 16 mosaicism: A review

Abstract

A review of all prenatal and postnatal diagnoses of trisomy 16 and trisomy 16 mosaicism was carried out in the context of the current understanding of confined placental mosaicism and uniparental disomy (UPD). The prenatal detection of trisomy 16 cells is associated with a high probability of fetal death, preterm delivery, intrauterine growth retardation, and fetal anomalies. Birth defects were typical of those seen in nonmosaic partial duplications of chromosome 16. Surprisingly, anomalies were sometimes limited to a single organ and included some relatively common isolated defects such as a ventricular septal defect, hypospadias, imperforate anus, inguinal hernia, and clubfoot. The risk for abnormality appeared to be higher in those pregnancies in which trisomy 16 cells were identified in amniotic fluid compared to the detection in chorionic villi samples. Contrary to nonmosaic trisomy 16 with an excess of males, mosaic trisomy 16 shows an excess of female karyotypes. Following the prenatal detection of trisomy 16 cells, aneuploid cells are almost never found in fetal or neonatal lymphocytes. Studies on fibroblasts also often fail to confirm the presence of the abnormal cell line even in cases in which multiple anomalies are present. It is likely that trisomy 16 cells are sometimes present in the early developing embryo even though subsequent cytogenetic studies on fetal or neonatal tissues may not detect any aneuploid cells. UPD can be excluded as a mechanism for those anomalies that are common to mosaic trisomy 16 and nonmosaic partial duplications. The term "occult mosaicism" is suggested to describe the situation in which the presence of an abnormal cell line is suspected on the basis of clinical data but unproven by laboratory analysis.

Embryonic delay in growth and development related to confined placental trisomy 16 mosaicism, diagnosed by I-Space Virtual Reality

“…All five pregnancies were complicated by fetal growth retardation. Other studies have also shown extremely high levels of hCG (2,22). Our patient, however, displayed an hCG level within the normal range on first trimester screening; the AFP level was also within the normal range (26 IU/mL, measured at 16 weeks in amniotic fluid; normal range, 15-30 IU/mL).…”

“…In trisomy 16, an early embryonic arrest usually results in a miscarriage between 8 and 15 weeks of gestational age. Trisomy 16 miscarriages show empty sacs, disorganized embryos, or minimal embryonic development (2). Almost all cases of trisomy 16 surviving in the second trimester of pregnancy are found to be mosaic (meaning that the cell lines contain both euploid and trisomic cells) (5).…”

Low incidence of UPD in spontaneous abortions beyond the 5th gestational week

“…By our approach it was not possible to detect low level trisomy in the placenta or in the foetus, taking into consideration that trisomic cells, may be confined to only one tissue compartment. 17 A phenotypic effect of maternal UPD(9) seems to be unlikely since there is no evidence for an imprinting locus on maternal chromosome 9 (Table 3). Therefore, maternal UPD(9) appears to be without major clinical consequences unless a recessive mutation is reduced to homozygosity, 18,19 whereas trisomy 9 mosaicism results in severe congenital anomalies.…”

Increased Nuchal Translucency and Early Growth Retardation Related to Confined Placental Mosaicism of Trisomy 16 in a Dichorionic Twin

“…Trisomy 16 is the most common autosomal trisomy of spontaneous abortions during the first trimester, and approximately 1% of clinically diagnosed conceptions are predicted to exhibit trisomy 16 [1]. Among trisomy 16 diagnoses, confined placental mosaicism (CPM) of trisomy 16 is defined as pregnancies wherein trisomy 16 cells are exclusively localized to the placenta.…”