Presentation on theme: "1 QF-PCR stand-alone prenatal diagnosis: the initial London experience. Caroline Mackie Ogilvie Cytogenetics Department Guy’s Hospital London."— Presentation transcript:
1 QF-PCR stand-alone prenatal diagnosis: the initial London experience. Caroline Mackie Ogilvie Cytogenetics Department Guy’s Hospital London
2 Guy’s QF-PCR data 2000 - 2007 Total samples tested: 23,311 CVS6729 (28.9%) AF16582 (71.1%) 97% of samples receive a result within one working day
3 Should we karyotype pregnancies at risk of Down syndrome? 32,674 pregnant women having invasive PND in London/South East 24,891 (76.2%) were referred for exclusion of Down syndrome others at risk of single gene disorders or complex chromosome abnormalities
4 24,891 pregnancies referred for exclusion of T21 118 sex chromosome abnormalities 153 other abnormalities
5 Good prognosis : – balanced rearrangements – variant regions Uncertain prognosis : – small marker chromosomes – mosaic anomalies Poor prognosis – non-mosaic genomic imbalance Abnormal karyotypes:
7 Poor Prognosis n = 18 1 liveborn (10q del) minor facial dysmorphism but normal development at 20 months 2 miscarried 4 outcome unknown, of which 1 = T16, 2 = 46,XX,del(18), 1=46,XX,add(9) 11 TOP (61%)
9 Advantages of QF-PCR stand-alone testing uncertain or harmless karyotypes not detected, reducing anxiety and follow-up studies no residual anxiety while waiting for karyotype results better use of resources
10 New service May 2007 All abnormal QF-PCR results followed up by karyotype analysis
11 Criteria for karyotyping Clinical indication, viz: structural abnormality on U/S 2 or more soft markers for trisomy 21 nuchal measurement >3mm at below 14 weeks gestation nuchals measurement >6mm for gestations >= 14 weeks family history of chromosome rearrangement
12 Data from 3 London labs 01/05/2007 – 30/11/2007 Consortium samples only
15 Abnormalities not detected by QF-PCR Detection rate in karyotyped AF3% Detection rate in karyotyped CVS7% No abnormal babies reported to date.
16 One pregnancy: QF-PCR only at CVS ultrasound showed severe IUGR and abnormal placenta at 26 weeks follow-up amnio: mos tetraploidy pregnancy terminated fetal blood showed normal karyotype Tetraploid cell line probably confined to placenta leading to placental insufficiency Abnormalities not detected by QF-PCR
17 NT >3mm 3mm<4mm “An alternative strategy whereby qf-PCR is the main method of analysis and full karyotyping is reserved for those cases with a minimum fetal NT thickness of 4 mm would require full karyotyping in 10.1% of the cases, would identify 99.0% of the significant abnormalities, and would cost 60% less than full karyotyping for all.” Chitty et al. (2006) BMJ 25;332(7539):452-5.
19 NT >3mm 3mm<4mm 2 abnormal karyotypes in this group 47,XY,+22 47,XX,+mar/46,XX –v small non-satellited marker, apparently all heterochromatin –?CPM –follow-up amnio and parental bloods requested, but not forthcoming –pregnancy terminated