Cytogenetic follow-up of chromosomal mosaicism detected in first-trimester prenatal diagnosis.

OBJECTIVE: To contribute to the risk assessment of true fetal mosaicism after detection of a mosaic chromosomal anomaly in chorionic villus samples (CVS) in order to enable more effective counseling and pregnancy management. METHODS: We retrospectively reviewed 7112 consecutive CVS analyzed on both direct preparations and cultured cells. In 135 out of the 177 cases of mosaicism, we performed cytogenetic follow-up and determined the frequency of confined placental mosaicism (CPM) and true fetal mosaicism according to type and distribution of the cytogenetic abnormality. RESULTS: True fetal mosaicism was detected in 38 out of 135 cases (28.15%), confirming the higher incidence of CPM (71.85%). Confirmation rate of CV mosaicism depends on the combination of placental cell lineages affected, chromosome involved and mosaic versus non-mosaic chromosomal anomaly. The overall probability of fetal involvement significantly rises with involvement of mesenchymal cells: 5.88% abnormal cytotrophoblast, 20.96% abnormal mesenchyme and 58.97% anomalies in both tissues. CONCLUSION: Most of the mosaic findings at CVS are unreliable indicators of the fetal karyotype. Our study contributes to large series with cytogenetic information from the different tissues along the cytotrophoblast-extraembrional mesoderm-fetus axis in order to infer clinical relevance of the findings and to enable more effective genetic counseling.

Structural chromosomal abnormalities detected during CVS analysis and their role in the prenatal ascertainment of cryptic subtelomeric rearrangements.

Mosaic structural chromosomal abnormalities observed along the trophoblast-mesenchyme-fetal axis, although rare, pose a difficult problem for their prognostic interpretation in prenatal diagnosis. Additional issues are raised by the presence of mosaic imbalances of the same chromosome showing different sizes in the different tissues, that is, deletions and duplications in the cytotrophoblast and mesenchyme of chorionic villi (CV). Some of these cytogenetic rearrangements originate from the post-zygotic breakage of a dicentric chromosome or of the product of its first anaphasic breakage. Selection of the most viable cell line may result in confined placental mosaicism of the most severe imbalance, favoring the presence of the cell lines with the mildest duplications or deletions in the fetal tissues. We document three cases of ambiguous results in CV analysis due to the presence of different cell lines involving structural rearrangements of the same chromosome which were represented differently in the trophoblast and the mesenchyme. Observation by conventional karyotype of a grossly rearranged chromosome in one of the CV preparations (direct or culture) was crucial to call attention to the involved chromosomal region in other tissues (villi or amniotic fluid), allowing the prenatal diagnosis through molecular cytogenetic methods of subtelomeric rearrangements [del(7)(q36qter); del(11)(q25qter); del(20)(p13pter)]. This would have surely been undiagnosed with the routine banding technique. In conclusion, the possibility to diagnose complex abnormalities leading to cryptic subtelomeric rearrangements, together with a better knowledge of the initial/intermediate products leading to the final abnormal cryptic deletion should be added to the advantages of the CV sampling technique.