Interpretation of chromosome mosaicism and discrepancies in chorionic villi studies

Sachs, E. S.; Jahoda, M. G. J.; Los, Frans J.; Pijpers, L.; Reuss, A.; Wladimiroff, J. W.

doi:10.1002/ajmg.1320370222

Cited by 33 publications

(22 citation statements)

References 16 publications

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“…Our data show that CVS was an accurate method for prenatal detection of fetal chromosomal abnormalities in laboratories reporting to EUROMIC in 1986-1992. The frequencies of CPM of 1-2 per cent found in other, smaller studies (Breed et al, 1990;Sachs et al, 1990;MRC Working Party, 1991;Ledbetter et al, 1992;Teshima et al, 1992;Wang et al, 1993;Pittalis et al, 1994; Association of Clinical Cytogeneticists Working Party on Chorionic Villi in Prenatal Diagnosis, 1994) are consistent with the 1·0 per cent frequency in the present series. Also, figures on the diagnostic accuracy of CVS in previous, smaller studies are comparable to the sensitivity, specificity, and negative predictive value of close to 100 per cent and the positive predictive value of about 75 per cent in our study.…”

Section: Accuracysupporting

confidence: 91%

Accuracy of cytogenetic findings on Chorionic Villus Sampling (CVS)—diagnostic consequences of CVS Mosaicism and non-Mosaic Discrepancy in Centres contributing to EUCROMIC 1986–1992

1997

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Of 62 865 karyotyped chorionic villus (CV) samples that were reported to EUCROMIC 1986–1992, 98.5 per cent showed either a normal karyotype (true negative result; 94.8 per cent of the total) or a non‐mosaic chromosomal aberration (true positive non‐mosaic result; 3.7 per cent). True fetal mosaicism was diagnosed in about 0.15 per cent of the 62 865 CV samples, while confined placental mosaicism (CPM) occurred in 1.0 per cent. False‐positive non‐mosaic aberrations were observed in 0.15 per cent and false‐negative CVS (chorionic villus sampling) results in only 0.03 per cent. The remaining 0.15 per cent of the CVS results were unclassifiable. These figures determined a sensitivity of CVS for prenatal detection of chromosome aberrations of 98.9–99.6 per cent (95 per cent confidence intervals), a specificity of 98.5–98.8 per cent, a positive predictive value of 72.6–78.3 per cent, and a negative predictive value of 99.95–99.98 per cent. False‐positive non‐mosaic aberrations that could not from the outset be suspected of being confined to the placenta were very rare (0.07 per cent of CV samples). They most often involved non‐mosaic monosomy X and trisomy 18 encountered after direct preparation alone. False‐negative CVS results were extremely rare (0.03 per cent) and occurred, with only one exception, after direct preparation alone. Thirteen of the 19 false‐negative CVS diagnoses were from pregnancies at a particularly high risk for fetal chromosomal aberration. Seventy‐five per cent of the pregnancies with CVS mosaicism or non‐mosaic discrepancy and known outcome continued to livebirth. When CVS mosaicism was encountered, the definitive prenatal cytogenetic diagnosis was most often obtained through subsequent amniocentesis. However, the use of amniocentesis and the frequency of pregnancy termination depended on the type of chromosomal aberration involved. We conclude that CVS is an accurate method for prenatal chromosome analysis. In pregnancies at high risk for fetal chromosomal abnormality, we recommend, however, not relying solely on a normal karyotype obtained after direct preparation alone. © 1997 John Wiley & Sons, Ltd.

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Section: Accuracysupporting

confidence: 91%

Accuracy of cytogenetic findings on Chorionic Villus Sampling (CVS)—diagnostic consequences of CVS Mosaicism and non-Mosaic Discrepancy in Centres contributing to EUCROMIC 1986–1992

1997

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“…Such a restrictive policy of discarding STC-villi and using only LTC-villi has been reported by Smidt-Jensen et al (1993). Another restrictive policy is the routine cytogenetic investigation in STC-villi, and in the case of an abnormality the additional investigation of LTC-villi, which has also been implemented in our laboratory for some years (Breed et al, 1990;Sachs et al, 1990;Leschot et al, 1996). We stopped the culturing and potential investigation of LTC-villi in 1993 since less than one per cent of the initiated cultures were actually investigated and in the majority of cases, LTC-villi turned out to be non-available when needed.…”

Section: Introductionmentioning

confidence: 93%

Abnormal karyotypes in semi-direct chorionic villus preparations of women with different cytogenetic risks

et al. 1998

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Among 3499 cytogenetically investigated semi‐direct chorionic villus samples, 219 (6·3 per cent) abnormal karyotypes were encountered. The karyotypes were considered certainly abnormal (generalized abnormal with high probability) in 109 cases (3·1 per cent), and in 110 cases (3·1 per cent) uncertainly abnormal (potentially confined to the placenta), requiring further investigation. Of these 110 uncertain abnormalities, the cytogenetic result turned out to be finally abnormal representing generalized abnormality in 36 cases (32·7 per cent), finally normal representing confined placental mosaicism (CPM) in 69 cases (62·7 per cent), and remained undetermined in 5 instances (4·5 per cent). The rate of the numbers of certainly abnormal and all (certainly+uncertainly) abnormal results, the certainty rate, and that of generalized abnormalities and all abnormalities (generalized abnormalities+CPM cases), the predictive value, are strongly correlated with the cytogenetic risk. Therefore, we advise chorionic villus sampling for cytogenetic investigation only in women with a cytogenetic risk equal to or exceeding that of a 40‐year‐old pregnant woman. Because of the high rate of prenatal follow‐up investigations after the finding of uncertain results in semi‐direct villi, semi‐direct and cultured villi should be karyotyped simultaneously. Copyright © 1998 John Wiley & Sons, Ltd.

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“…In our series, there were no examples of false-positive diagnoses involving the common trisomies (21, 18, or 13) among 44 cases with cytogenetic follow-up from fetal tissues. The four reported cases of false-positive diagnosis of trisomy 18 by the direct method (Mikkelsen, 1985;Sachs et al, 1990;Leschot et al, 1990) still cause some concern, however, when acting upon information from the direct method alone. We encountered one case of apparent false-positive diagnosis of 47,XXX by the direct method: cultured cells and fetal tissue after termination showed only normal 46,XX cells.…”

Section: Non-mosaic Aneuploidiesmentioning

confidence: 99%

Cytogenetic results from the U.S. collaborative study on CVS

Ledbetter¹,

Zachary²,

Simpson³

et al. 1992

Prenatal Diagnosis

321

223

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Cytogenetic data are presented for 11,473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male.(ABSTRACT TRUNCATED AT 400 WORDS)

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Interpretation of chromosome mosaicism and discrepancies in chorionic villi studies

Cited by 33 publications

References 16 publications

Accuracy of cytogenetic findings on Chorionic Villus Sampling (CVS)—diagnostic consequences of CVS Mosaicism and non-Mosaic Discrepancy in Centres contributing to EUCROMIC 1986–1992

Accuracy of cytogenetic findings on Chorionic Villus Sampling (CVS)—diagnostic consequences of CVS Mosaicism and non-Mosaic Discrepancy in Centres contributing to EUCROMIC 1986–1992

Abnormal karyotypes in semi-direct chorionic villus preparations of women with different cytogenetic risks

Cytogenetic results from the U.S. collaborative study on CVS

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