BACKGROUND: In 2004, the UK National Screening Committee (UKNSC) recommended that new screening programmes for Down's syndrome need not include karyotyping and can offer prenatal diagnosis for the syndrome with FISH (fluorescence in-situ hybridisation) or PCR as rapid diagnostic tests. The UKNSC also recommended that FISH or PCR tests should only include trisomies 13, 18, and 21. We undertook a retrospective cytogenetic audit to assess the probable clinical effect of these proposed policy changes. METHODS: 23 prenatal cytogenetic laboratories from the UK public sector submitted data for amniotic fluid or chorionic villus samples referred from April, 1999, to March, 2004. We obtained data for the details of all abnormal karyotypes by reason for referral and assessed the efficiency of FISH and PCR rapid tests for the detection of chromosome abnormalities. FINDINGS: Of 119,528 amniotic fluid and 23,077 chorionic villus samples, rapid aneuploidy testing replacement of karyotyping would have resulted in about one in 100 and one in 40 samples having an undetected abnormal karyotype, respectively. Of these missed results, 293 (30%) of 1006 amniotic fluid samples and 152 (45%) of 327 chorionic villus samples were associated with a substantial risk of an abnormal phenotypic outcome. Of 34,995 amniotic fluid and 3049 chorionic villus samples that had karyotyping and a rapid test on the same sample, none of the three technologies was completely reliable to detect an abnormal karyotype, but the best protocol for an interpretable result was PCR and karyotyping or FISH and karyotyping. INTERPRETATION: Replacement of full karyotyping with rapid testing for trisomies 13, 18, and 21 after a positive screen for Down's syndrome will result in substantial numbers of liveborn children with hitherto preventable mental or physical handicaps, and represents a substantial change in the outcome quality of prenatal testing offered to couples in the UK.
BACKGROUND: In 2004, the UK National Screening Committee (UKNSC) recommended that new screening programmes for Down's syndrome need not include karyotyping and can offer prenatal diagnosis for the syndrome with FISH (fluorescence in-situ hybridisation) or PCR as rapid diagnostic tests. The UKNSC also recommended that FISH or PCR tests should only include trisomies 13, 18, and 21. We undertook a retrospective cytogenetic audit to assess the probable clinical effect of these proposed policy changes. METHODS: 23 prenatal cytogenetic laboratories from the UK public sector submitted data for amniotic fluid or chorionic villus samples referred from April, 1999, to March, 2004. We obtained data for the details of all abnormal karyotypes by reason for referral and assessed the efficiency of FISH and PCR rapid tests for the detection of chromosome abnormalities. FINDINGS: Of 119,528 amniotic fluid and 23,077 chorionic villus samples, rapid aneuploidy testing replacement of karyotyping would have resulted in about one in 100 and one in 40 samples having an undetected abnormal karyotype, respectively. Of these missed results, 293 (30%) of 1006 amniotic fluid samples and 152 (45%) of 327 chorionic villus samples were associated with a substantial risk of an abnormal phenotypic outcome. Of 34,995 amniotic fluid and 3049 chorionic villus samples that had karyotyping and a rapid test on the same sample, none of the three technologies was completely reliable to detect an abnormal karyotype, but the best protocol for an interpretable result was PCR and karyotyping or FISH and karyotyping. INTERPRETATION: Replacement of full karyotyping with rapid testing for trisomies 13, 18, and 21 after a positive screen for Down's syndrome will result in substantial numbers of liveborn children with hitherto preventable mental or physical handicaps, and represents a substantial change in the outcome quality of prenatal testing offered to couples in the UK.
Authors: Celia Badenas; Laia Rodríguez-Revenga; Carme Morales; Carmen Mediano; Alberto Plaja; Ma Mar Pérez-Iribarne; Anna Soler; Núria Clusellas; Antoni Borrell; Ma Ángeles Sánchez; Elisabeth Miró; Aurora Sánchez; Montserrat Milà; Wladimiro Jiménez Journal: J Mol Diagn Date: 2010-10-01 Impact factor: 5.568
Authors: Antina de Jong; Wybo J Dondorp; Daniëlle R M Timmermans; Jan M M van Lith; Guido M W R de Wert Journal: Eur J Hum Genet Date: 2011-06-01 Impact factor: 4.246
Authors: Antina de Jong; Wybo J Dondorp; Suzanna G M Frints; Christine E M de Die-Smulders; Guido M W R de Wert Journal: Nat Rev Genet Date: 2011-08-18 Impact factor: 53.242
Authors: Diane Van Opstal; Marjan Boter; Danielle de Jong; Cardi van den Berg; Hennie T Brüggenwirth; Hajo I J Wildschut; Annelies de Klein; Robert-Jan H Galjaard Journal: Eur J Hum Genet Date: 2008-09-10 Impact factor: 4.246
Authors: Elisabeth M A Boormans; Erwin Birnie; Hajo I Wildschut; Heleen G Schuring-Blom; Dick Oepkes; Carla A C van Oppen; Jan G Nijhuis; Merryn V E Macville; Angelique J A Kooper; Karin Huijsdens; Mariëtte V J Hoffer; Attie Go; Johan Creemers; Shama L Bhola; Katia M Bilardo; Ron Suijkerbuijk; Katelijne Bouman; Robert-Jan H Galjaard; Gouke J Bonsel; Jan Mm van Lith Journal: BMC Pregnancy Childbirth Date: 2008-05-20 Impact factor: 3.007