Chromosomal mosaicism in chorionic villus sampling

Abstract

The observation of multiple, chromosomally distinct cell lines in chorionic villus samples is not an unusual finding and occurs in 1 per 100 samples. This frequency is ten times greater than the level of mosaicism observed in newborn surveys and, thus, must reflect phenomenon other than true fetal mosaicism. Indeed, only 23% of mosaicism detected at CVS is confirmed in the fetus (2.3 per 1,000 CVS), which is much closer to the newborn rate (1 per 1,000). This indicates that most mosaicism encountered in CVS is unrelated to the fetal karyotype and as such is an inaccurate prediction of the fetal genotype, the purpose of prenatal diagnosis. Most of the mosaicism detected in CVS is due to confined placental mosaicism. Either as a result of error-prone cell division generating an excess of abnormal cells in extraembryonic tissues or reduced selection against aneuploid cells in these tissues allowing their persistence, chorionic villi and placenta appear to show much higher levels of mosaicism than seen in fetuses. This explains the more frequent finding of multiple cell lines in CVS than in amniocentesis or liveborn individuals. The discrepancy between levels of mosaicism present in chorionic villi and fetal tissues means that most instances of mosaicism detected in CVS are not associated with a fetal abnormality and should be evaluated by further prenatal testing, i.e., amniocentesis or fetal blood sampling. Because of the frequency of chromosomal mosaicism in CVS and its attendant need for further testing, a discussion of mosaicism should be included in counseling prior to CVS. The higher frequency of discrepant results in direct CVS preparation emphasizes the prudence of delaying decision making until the results of the CVS culture have been obtained. Although the observation of mosaicism clearly complicates genetic counseling and decision making, it does not appear to be associated with an adverse fetal outcome. Whereas most of the mosaicism observed in CVS is the result of confined placental mosaicism, other types of discrepancies also occur. Maternal cell contamination occurs in about 1% of cases, but is easily evaluated by examining the direct preparation and analyzing chromosome polymorphism. The incidence of pseudomosaicism in CVS cultures is unclear but probably low. Interestingly, CVS analysis has suggested that twinning may be a more common phenomenon at conception than reported at birth and that some discrepancies may reflect the nonviability of twins with abnormal karyotypes. Chorionic villi sampling remains a viable alternative to amniocentesis for early prenatal diagnosis. An understanding of the origins of mosaicism in CVS is necessary for