Rapid aneuploidy screening with fluorescence in-situ hybridisation: is it a sufficiently robust stand-alone test for prenatal diagnosis?
OBJECTIVE
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.


METHODS
Retrospective analysis.


METHODS
A restructured Government hospital in Singapore and an academic hospital in the United States.


METHODS
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.


CONCLUSIONS
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.
Cytogenetics Laboratory, Department of Pathology, Singapore General Hospital, Singapore. alvin.lim.s.t@sgh.com.sg
A S T
AS
Lim
T H
TH
Lim
M M
MM
Hess
S K
SK
Kee
Y Y F
YY
Lau
R
R
Gilbert
T E
TE
Hempel
K J
KJ
Anderson
D H
DH
Zaleski
S L
SL
Tien
P
P
Chia
R
R
Subramaniam
H K
HK
Tan
A S A
AS
Tan
W G
WG
Sanger
D000328:Adult; D000782:Aneuploidy; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008423:Maternal Age; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies