False-negative findings in chorionic villus sampling. An experimental approach and review of the literature.
61 fetuses/newborns who had an aberrant karyotype in amniocentesis (AC) or percutaneous umbilical blood sampling (PUBS) were followed-up by chorionic villus sampling (CVS) at birth or after interruption. The overall rate of discrepancies is surprisingly high. Among 46 cases with a non-mosaic numerical aberration an AC or PUBS three had a discrepant finding in placental tissue. This was also true in one of seven cases with non-mosaic structural aberrations and in three of five cases with mosaic structural aberrations. All three cases with a mosaic numerical aberration in AC or PUBS were not represented by CVS and/or lymphocytes or fibroblasts, demonstrating the general problem of the unpredictable prognostic value of mosaicism. Our data suggest, that in case of prenatal diagnosis by CVS, using a combined procedure of short-term (STC) and long-term culture (LTC), in our sample we would have missed one case of 45,X (1.6 per cent). When relying only on STC another two cases, one with 47, +21 and one with 46,XX,der(22) would not have been recognized (4.9 per cent, n = 3). All other chromosome aberrations would have been detected by STC alone. On the other hand, one case of 45,X was 'nearly missed' because of low-grade mosaicism in AC (45,X[1]/46,XX[19]), whereas in placental tissues and PUBS only 45,X was represented. This study mimics a false-negative rate of about 1:3000 (STC plus LTC) or about 1:1000 (STC alone) for an a priori risk group of two per cent (e.g., advanced maternal age).
Kennerknecht
I
I
Abteilung Medizinische Genetik der Universität Ulm, Germany. ingo.kennerknecht@medizin.uni-ulm.de
Barbi
G
G
Djalali
M
M
Mehnert
K
K
Schneider
M
M
Terinde
R
R
Vogel
W
W
D000328:Adult; D000649:Amniocentesis; D002824:Chorionic Villi / Q000473:pathology; D015193:Chorionic Villi Sampling; D002869:Chromosome Aberrations / Q000175:diagnosis* / Q000235:genetics; D025063:Chromosome Disorders; D005188:False Negative Reactions; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D009030:Mosaicism; D011247:Pregnancy