RESUMO
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)(q10;q10)[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.