Mosaic Trisomy 21 on CVS With a Discordant Ultrasound
A 38-year-old G1 at 12 weeks undergoes chorionic villus sampling for advanced maternal age. Direct cytogenetic preparation (cytotrophoblast) shows 47,XX,+21 in 6 of 20 cells; cultured villi (mesenchymal core) show 46,XX in 20 of 20 cells. Fetal ultrasound at 13 weeks shows a normal nuchal translucency and no structural anomalies. The laboratory reports 'mosaic trisomy 21, confined placental mosaicism cannot be excluded.' The patient is anxious and wants a definitive answer. The MFM team asks whether amniocentesis is needed and what the recurrence risk is.
1. Interpret the discordance between direct and cultured preparations and advise on next steps.
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The pattern - abnormal direct (cytotrophoblast) with normal cultured (mesenchymal core) - is the classic signature of confined placental mosaicism (CPM) type I/III depending on the distribution. The cytotrophoblast derives from the outer cell mass and the mesenchymal core from the inner cell mass, so discordance can reflect a trisomic zygote that lost the trisomy in the fetal lineage (true fetal mosaicism with low-level trisomy) or a trisomy confined to placenta.
Because the cultured villi (which better reflect the fetus) are normal, the finding is reassuring but not definitive. The appropriate next step is amniocentesis with uncomplicated FISH for chromosomes 13/18/21 and karyotype or microarray on amniocytes. Amniocytes derive from the fetal lineages and are the appropriate tissue for fetal diagnosis. The patient should be counseled that CPM is common and often benign, but that low-level true fetal mosaicism cannot be excluded without amniocentesis, and that a normal amniocentesis substantially reduces but does not eliminate concern.
2. What recurrence risk should be quoted, and how does it differ from a non-mosaic trisomy 21?
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For a mosaic trisomy 21 detected on CVS with a normal fetal karyotype (CPM), the recurrence risk is low - generally quoted as approximately 1% or the age-related risk, not the ~1% empiric recurrence associated with a prior non-mosaic trisomy 21 pregnancy. The distinction matters: the family should not be given the higher recurrence figure appropriate to a confirmed fetal aneuploidy.
Caveats: if amniocentesis shows true fetal mosaicism, recurrence risk counseling changes and the family should be referred for genetics follow-up. If the trisomy were due to a parental balanced Robertsonian translocation (unlikely here given normal parents and no prior history, but should be considered if recurrent), the risk would be different. In this scenario, no parental karyotype is indicated based on a single CPM finding, but recurrence and future prenatal screening should be discussed.
3. The patient asks whether the 'mosaic' result means her baby could have Down syndrome features. How should this be answered?
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Explain that the mosaic result came from the placenta, not necessarily the baby. If the amniocentesis is normal, the placental finding is most likely confined to the placenta and the fetus is expected to be unaffected. If true fetal mosaicism is present, the phenotype depends on the level and tissue distribution of the trisomic cells; low-level mosaicism can be associated with milder or no features, but outcomes are variable and cannot be predicted precisely from a percentage.
Avoid overreassurance before amniocentesis, and avoid catastrophizing. Set expectations: a normal amniocentesis is strongly reassuring; a mosaic amniocentesis would prompt detailed counseling and possibly further imaging. Offer follow-up with a genetic counselor after the amniocentesis result and note that the patient can decline further testing if she prefers, understanding the residual uncertainty.