An epidemiological study of holoprosencephaly from a regional congenital anomaly register: 1995-2004

Objective To investigate complete discrepancies in the prenatal diagnosis of trisomy 21 between QF-PCR analysis of uncultured villi and karyotyping of cultured cells in three chorion villus samples. Methods Clinical details were obtained from all three patients. Follow-up studies were undertaken where possible by evaluation of chromosome 21 copy number with QF-PCR, interphase FISH, MLPA and karyotyping, and by post-mortem examination. Results Case 1: severe oligohydramnios and microcephaly on scan. QF-PCR: trisomy 21; MLPA: trisomy 21; cultured karyotype: 46,XY[48]. Placental and fetal tissue results and post-mortem examination indicated a euploid fetus with trisomy 21 mosaicism confined to the placenta. Case 2: Down screen risk 1 : 16; NT = 4.4 mm; absent nasal bone (Caucasian mother). QF-PCR: disomy 21; cultured karyotype: 47,XY,+21[23]. Neck thickening noted at delivery-post-mortem refused, no fetal tissue available. Placental tissue indicated mosaicism for trisomy 21. Case 3: Down screen risk 1: 91; NT = 6.7 mm. QF-PCR: disomy 21; cultured karyotype: 46,XX,der(21;21)(q 10;q 10)[60]. No follow-up possible. PCR genotyping of cultured cells confirmed sample identity in all three cases. Chromosome 21 markers observed by PCR were biallelic in all three cases, indicating that a mitotic error could account for the presence of the abnormal cell lines in each case. Conclusion QF-PCR analysis of uncultured villi and cultured karyotyping may rarely show complete discrepancy in the prediction of fetal trisomy 21 in CVS. Within-biopsy sample mosaicism, together with the testing of different cell populations, provide an explanation for these results. Practical ways to minimise the risk of such discrepancy are proposed. Copyright (c) 2007 John Wiley & Sons, Ltd.