Complete trisomy 21 vs translocation Down syndrome:
a comparison of modes of ascertainment
Eran Bornstein, MD; Erez Lenchner, MS; Alan Donnenfeld, MD; Cristiano Jodicke, MD;
Sean M. Keeler, MD; Sara Kapp, MS, CGC; Michael Y. Divon, MD
OBJECTIVE: To compare the indications for invasive prenatal testing
resulting in the detection of translocation Down syndrome and complete
trisomy 21.
STUDY DESIGN: This case control study was based on a large amnio-
centesis and chorionic villi samples database (n = 534,795). All spec-
imens with translocation Down syndrome (n = 203) comprised the
translocation group and were compared with a maternal age-matched
group (4 to 1, n = 812) in which complete trisomy 21 was detected.
Women with a normal karyotype were randomly selected (n = 812) and
served as controls. Indications for invasive testing were compared
among the 3 paired groups using
2
analysis.
RESULTS: There were no differences in the incidence of abnormal first-
and second-trimester screening tests between the translocation Down
syndrome and the complete trisomy 21 groups. History of prior aneu-
ploidy was significantly more frequent in the translocation Down syn-
drome group, as compared with either complete trisomy 21 fetuses or
normal controls.
CONCLUSION: Fetuses with translocation Down syndrome present with
the same screening abnormalities as fetuses with complete trisomy 21.
Key words: Down syndrome, prenatal diagnosis, translocation,
trisomy 21
Cite this article as: Bornstein E, Lenchner E, Donnenfeld A, et al. Complete trisomy 21 vs translocation Down syndrome: a comparison of modes of ascertainment.
Am J Obstet Gynecol 2010;203:391.e1-5.
D
own syndrome (DS) is a major
cause of mental retardation, affect-
ing 1 in 800 newborns.
1,2
Approximately
95% of DS cases are caused by the pres-
ence of 3 copies of chromosome 21
(complete T21). This is most frequently
the result of a maternal meiotic nondis-
junction of the chromosome 21 pair.
3,4
Less common forms of genetic aberra-
tions that account for the remainder of
DS cases include mosaicism of trisomy
21 and translocations involving chromo-
some 21. Each of these aberrations is
thought to account for approximately
1-3% of all DS cases.
5-7
Extensive research in prenatal screen-
ing for DS has led to major advance-
ments in our ability to identify affected
fetuses during the first and second tri-
mesters.
8-20
These first- and second-tri-
mester screening modalities use mater-
nal serum analytes and fetal sonographic
evaluation to modify the a priori, age-
related risk for DS, and provide an indi-
vidual, patient-specific risk assessment.
Several protocols for combining these
screening tests are now available (known
as sequential, integrated, or contingent
testing) and have been shown to signifi-
cantly improve the detection rate of DS
(90%), whereas, decreasing the screen
positive rate to approximately 3%.
14-16
Sonographic evaluation of the fetus in
the second trimester can detect both major
anomalies as well as characteristic soft
markers associated with DS. This “genetic
ultrasound” has been associated with a de-
tection rate of 50-70% of DS fetuses.
17-20
It
is, however, also associated with a substan-
tial screen positive rate.
Whereas an increase in maternal age is
directly associated with an increased risk
of complete T21, there is no such associ-
ation in cases of translocations leading to
DS (Trans-DS). Approximately 25% of
unbalanced Robertsonian translocations
that result in DS are inherited from a
translocation carrier parent, and are
therefore associated with a high recur-
rence rate.
4
The extensive research that has been
dedicated to DS screening has focused pri-
marily on the detection of fetuses with a
complete T21 karyotype. A paucity of data
exist regarding the prenatal detection of
the less common forms of DS. Recently, we
demonstrated that fetuses with mosaicism
of trisomy 21 do not present with the same
abnormal screening tests as fetuses with
complete T21.
21
However, data regarding
the prenatal detection of fetuses with
Trans-DS are still lacking. Therefore, the
objective of our study was to analyze the
indications for invasive prenatal testing
leading to the detection of fetuses with
Trans-DS and compare them with those of
complete T21 and chromosomally normal
fetuses.
MATERIALS AND METHODS
We conducted a retrospective case con-
trol study to compare the major indica-
From the Division of Maternal-Fetal
Medicine, Department of Obstetrics and
Gynecology (Drs Bornstein and Keeler), and
the Human Genetics Program (Ms Kapp),
New York University School of Medicine;
the Statistics and Mapping Laboratory (Mr
Lenchner), New York University; and the
Department of Obstetrics and Gynecology
(Dr Divon), Lenox Hill Hospital, New York,
NY; Genzyme Genetics (Dr Donnenfeld),
Philadelphia, PA; and the Division of
Maternal-Fetal Medicine, Department of
Obstetrics and Gynecology (Dr Jodicke),
Wayne State University School of Medicine,
Detroit, MI.
Presented at the 30th Annual Meeting of the
Society for Maternal-Fetal Medicine, Chicago,
IL, Feb. 1- 6, 2010.
Received Feb. 26, 2010; revised April 30,
2010; accepted June 7, 2010.
Reprints not available from the authors.
0002-9378/$36.00
© 2010 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2010.06.019
SMFM Papers www. AJOG.org
OCTOBER 2010 American Journal of Obstetrics & Gynecology 391.e1