Is routine karyotyping required in prenatal samples with a molecular or metabolic referral?

As a routine, karyotyping of invasive prenatal samples is performed as an adjunct to referrals for DNA mutation detection and metabolic testing. We performed a retrospective study on 500 samples to assess the diagnostic value of this procedure. These samples included 454 (90.8%) chorionic villus (CV) and 46 (9.2%) amniocenteses specimens. For CV samples karyotyping was based on analyses of both short-term culture (STC) and long-term culture (LTC) cells. Overall, 19 (3.8%) abnormal karyotypes were denoted: four with a common aneuploidy (trisomy 21, 18 and 13), two with a sex chromosomal aneuploidy (Klinefelter syndrome), one with a sex chromosome mosaicism and twelve with various autosome mosaicisms. In four cases a second invasive test was performed because of an abnormal finding in the STC. Taken together, we conclude that STC and LTC karyotyping has resulted in a diagnostic yield of 19 (3.8%) abnormal cases, including 12 cases (2.4%) with an uncertain significance. From a diagnostic point of view, it is desirable to limit uncertain test results as secondary test findings. Therefore, we recommend a more targeted assay, such as e.g. QF-PCR, as a replacement of the STC and to provide parents the autonomy to choose between karyotyping and QF-PCR.