Hong Kong Med J 2010;16:427–33 | Number 6, December 2010
Rapid aneuploidy screening with fluorescence in-situ hybridisation: is it a sufficiently robust stand-alone test for prenatal diagnosis?
Alvin ST Lim, TH Lim, Michelle M Hess, SK Kee, Yvonne YF Lau, Rebecca Gilbert, Thomas E Hempel, Kirby J Anderson, Dianna H Zaleski, SL Tien, Patrick Chia, Raman Subramaniam, HK Tan, Ann SA Tan, Warren G Sanger
Cytogenetics Laboratory, Department of Pathology, Singapore General Hospital, Singapore
OBJECTIVES. To assess the clinical utility of fluorescence in-situ hybridisation with chromosomes 13, 18, 21, X and Y as a stand-alone test in detecting chromosomal abnormalities, and the types of chromosomal abnormalities missed.
DESIGN. Retrospective analysis.
SETTING. A restructured Government hospital in Singapore and an academic hospital in the United States.
PARTICIPANTS. Cytogenetic data of prenatal specimens and results of fluorescence in-situ hybridisation of 5883 patients performed between January 2000 and August 2007 were reviewed.
RESULTS. Fluorescence in-situ hybridisation detected 558 (9.5%) patients with chromosomal abnormalities. Abnormal ultrasounds (70%) and maternal serum screens (21%) were the most indicative of chromosomal abnormalities. When comparing fluorescence in-situ hybridisation data with karyotype results for the five chromosomes of interest, the sensitivity and specificity were 99.3% and 99.9%, respectively. When comparing fluorescence in-situ hybridisation data with karyotype results for all chromosomes, the sensitivity decreased to 86.8%, whereas the specificity remained at 99.9%. Of 643 cases with karyotype abnormalities, 85 were fluorescence in-situ hybridisation–negative (false negative rate, 13.2%), which included structural rearrangements, chromosome mosaicism, and other trisomies. Despite abnormal ultrasound indications, fluorescence in-situ hybridisation missed 32 cases which included structural rearrangements, mosaicisms, and other trisomies.
CONCLUSION. This study does not support fluorescence in-situ hybridisation as a stand-alone test. Institutions supporting fluorescence in-situ hybridisation as a stand-alone test must seriously consider the risks of a missed diagnosis.
Key words: Aneuploidy; In situ hybridization, fluorescence; Karyotyping; Prenatal diagnosis
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