Single
Autosomal
Monosomy
nosomy
with aneuploidy detected (AD) and/or
d (AS) for chromosomes 21,18,13, X and Y
with Sex
Chromosome
Abnormality1
Multiple
Aneuploidy1
Total
Cases Monosomy
66 and Multiple
35
37
138
Outcome Following Autosomal
Aneuploidy
as requested for all cases via:
Mean Maternal Age
34.4
37.3
35.3
35.4
Outcome
Following
Autosomal
Monosomy
and
Results
by Noninvasive
Prenatal
Screening
(years)
(19-‐46)
(24-‐47)
(23-‐44)
(19-‐47)
M
Results
by
Noninvasive
Prenatal
Scre
Holly Snyder, Patricia Devers, Patricia Taneja, Sucheta Bhatt
ng phone calls
Mean Gestational Age
(weeks)
Outcomes Received
nto one of three categories
Method
 
12
(18.2%)
4
(11.4%)
13
(10-‐34)
1
(2.7%)
(58.7%)
17
(12.3%)
Res
Includes AD and AS results
► Database query for all singleton NIPS samples during the study
► A recent study of cytogenetic analysis following spontaneous
2
EDD not passed at time of data collection
period with one of the following results:
miscarriage showed that 5% of samples were affected with a
– Single autosomal monosomy
multiple aneuploidy.1
– Multiple aneuploidy with aneuploidy detected (AD) and/or
► An estimated 0.16% of trisomy 21 cases involve a double
aneuploidy suspected (AS) for chromosomes 21,18,13, X and Y
aneuploidy with either XXX, XXY, XYY or MX. The combination of
► Outcome information was requested for all cases via:
Down syndrome and Klinefelter syndrome is the most common.2
• Fax requests
► Full autosomal monosomies are not generally compatible►
• Outgoing
incoming phone was
calls confirmed in 15
withOverall,
life;
full or
partialand
concordance
Multiple
Aneuploidy
however,
partial and
mosaic forms of autosomal monosomy have
(10.9%) cases
► Data on 138 samples was reviewed
been reported in liveborns
1
Summary of Findings
• Clinical hx: 33 y.o. with
► This study
► Results were classified into one of three categories
echogenic
intracardiac
evaluates outcomes
of clinical laboratory noninvasive
► An additional
13 (9.4%) cases were explained by other
prenatal
screening
(NIPS)
samples
from
singleton
pregnancies
focus and shortened long
biological etiologies, including maternal malignancy (7,
receiving multiple aneuploidy and/or autosomal monosomy results
bones on ultrasound
5.1%), maternal karyotype anomalies (1, 0.7%) or other
• NIPS result: aneuploidy
fetal karyotype anomalies (5, 3.6%)
detected for chromosomes
21 and 18
Figure• 1Prenatal dx: declined
Case Examples
► Some autosomal
monosomies were explained by
• Outcome: postnatal fetal
abnormalities in one of the reference chromosomes used to
Result Classification
Multiple Aneuploidy
Autosomal Monosomy
karyotype c/w 47,+21;
analyze
test
chromosomes
n=138
• Clinical hx: 33 y.o. with
• Clinical hx: 24 y.o. with
placental analysis c/w
echogenic intracardiac
Dandy Walker
mosaic trisomy 18
focus and shortened long
malformation on
26.8%
CONCORDANT
th
Conclusions
OTHER
hygroma and encephalocele
Figure on
2 ultrasound
 
• NIPS result: full/partial
dy
Outcomes
monosomy for
chromosome
omes
13
Single Trisomy
Single
Multiple
with Sex
Concordance
• PrenatalAutosomal
dx: declined
Chromosome Aneuploidy
Monosomy
• Outcome: TOP Abnormality
secondary to
Concordant
ultrasound 2findings;2 POC 1
CVS
Partially Concordant
0
3
7not
karyotype analysis
Y
Discordant
10
14
successful20
CBC
• Paternal karyotype:
Other
7
6 c/w
9
p
ocytic Outcome 46,XY
Unknown t(13;20)(q22:q31.1)
25
7
10
1
2
► We anticipate that a portion of multiple aneuploidy and
autosomal monosomy findings reflect the fetal karyotype
Monosomy
Multiple Aneuploidy
while some may
be explained by otherAutosomal
etiologies,
such as
• Clinical hx: 33 y.o. with cystic
•
Clinical
hx:
23
y.o.
with
other maternal/fetal chromosomal aberrations,
maternal
hygroma and encephalocele
unilateral multicystic
Total Cohort
disease, mosaicism
co-twin demise.on ultrasound
kidney on or
ultrasound
5
►
10
44
22
42
Outcome Unknown,
EDD Not Passed3
12
3
0
15
Total
66
35
37
138
• NIPS result: full/partial
• NIPS result: aneuploidy
monosomy for chromosome
detected for chromosomes
13
21 and 13; full/partial
Continued evaluation
of outcomes for complex
NIPS results
•
Prenatal
dx:
declined
monosomy for
is warranted to
better
understand
the
biological
reasons
forto
• Outcome: TOP secondary
chromosome 18
ultrasound findings; POC
such results • Prenatal diagnosis: CVS
karyotype analysis not
and Amnio c/w 46,XY
successful
• Outcome: Maternal CBC
• Paternal karyotype: c/w
and additional work-up
46,XY t(13;20)(q22:q31.1)
revealed acute lymphocytic
leukemia (ALL)
Me
(ye
Me
(we
Ou
ED
1
2
Inclu
EDD
Sum
►
►
►
Con
►
►
►
Concordance confirmed for one aneuploidy
Other outcomes include SAB/TOP/IUFD, maternal conditions and other reported fetal karyotype anomalies
3
EDD not passed as of data collection
1
2
References
1
Subramaniyam S, Pulijaal VR, Matthew S. Double and multiple chromosomal aneuploidies in spontaneous abortions: A single institutional experience. J Hum Reprod Sci. 2014 Oct-Dec; 7(4): 262–268. doi: 10.4103/0974-1208.147494
Kovaleva
NV,Mutton
DE. Epidemiology
of double
aneuploidies
involving chromosome 21 and the sex chromosomes. Am J Med Genet A. 2005 Apr 1;134A(1):24-32.
um Reprod Sci.
2014
Oct-Dec;
7(4): 262–268.
doi:
10.4103/0974-1208.147494
(1):24-32.
CONCORDANT
bones on ultrasound
ultrasound
•
NIPS result: aneuploidy
• NIPS result: full/partial
Single Trisomy with Sex Chromosome
detected for chromosomes
monosomy for
25.4%
Abnormality
21 and 18
chromosome 13
Multiple Aneuploidy
• Prenatal dx: declined
• Prenatal dx: declined
• Outcome: postnatal fetal
• Outcome:
term delivery
Autosomal Monosomy
cases,
abnormal NIPS
results relate to a
► Although in most
karyotype c/w 47,+21;
• Postnatal array: c/w
placental analysis c/w
single trisomy,
other
results
9.3Mb
deletion
on may be reported.
• Clinical hx: 33 y.o. with cystic
mosaic trisomy 18
chromosome 13q
Single Autosomal Monosomy (21, 18, 13)
47.8%
Cas
OTHER
d
ery
Introduction
EDD not yet passed2
Illumina,
USA
(43.9%) Redwood
(71.4%)City, CA,
(70.3%)
OTHER
al
14.0
(10-‐34)
CONCORDANT
th
12.0
(10-‐25)
Illumina,Holly
Redwood
City,
CA, USA
Snyder,
Patricia
Devers,25Patricia Taneja,
Sucheta
Bhatt
29
26
81
as reviewed
my
14.8
(10-‐32)
2
OutcomeScreening
Following Autosomal Monosomy and M
sive Prenatal
Results by Noninvasive Prenatal Scr
Single
Autosomal
Monosomy
nosomy
with aneuploidy detected (AD) and/or
d (AS) for chromosomes 21,18,13, X and Y
ers, Patricia Taneja, Sucheta Bhatt
Cases
Multiple
Aneuploidy1
Total
35
37
138
66
Holly Snyder, Patricia Devers, Patricia Taneja, Sucheta Bha
dwood City, CA, USA
as requested for all cases via:
Mean Maternal Age
(years)
Results
ng phone calls
with Sex
Chromosome
Abnormality1
34.4
37.3
35.3 USA
Illumina,
Redwood
City, CA,
(19-‐46)
 
Mean Gestational Age
14.8
Method(10-‐32)
  (weeks)
Sample Demographics by Result Classification
Introduction
(24-‐47)
(23-‐44)
35.4
(19-‐47)
12.0
(10-‐25)
14.0
(10-‐34)
13
(10-‐34)
ingleton NIPS samples during the study
as
reviewed
ollowing results:
25
26
81study
► Database29query for all singleton
NIPS samples
during the
► A recent study of cytogenetic analysis following spontaneous
Single
Trisomy
Outcomes
Received
Single
onosomy
Multiple
(43.9%)
(71.4%)
(70.3%)
(58.7%)
with
Sex
period with one of the following results:
miscarriage showed that 5% of samples were affected with
a
Autosomal
Total
Chromosome Aneuploidy1
with
aneuploidy
detected
(AD)
and/or
Monosomy
1
nto one of three
– Single autosomal monosomy
multiplecategories
aneuploidy.
Abnormality1
d (AS) for chromosomes 21,18,13, X and Y
12
4
1
17
2 – Multiple aneuploidy with aneuploidy detected (AD) and/or
EDD
Cases
66 not yet passed
35
37(18.2%) 138
(11.4%)
(2.7%) 21,18,13,
(12.3%)
► An estimated 0.16% of trisomy 21 cases involve a double
aneuploidy suspected
(AS) for chromosomes
X and Y
as requested foraneuploidy
all cases via:
Mean
Maternal
Age
34.4
37.3
35.3
35.4
with either XXX, XXY, XYY or MX. The combination of
(years)
(19-‐46) AD
(24-‐47)
(23-‐44)
(19-‐47)
2 and
Includes
AS results
► Outcome
information was requested for all cases via:
Down syndrome and Klinefelter syndrome is the most 1common.
2
EDD
not
passed
at
time
of
data
collection
ng phone calls
• Fax
Mean Gestational Age
14.8
12.0
14.0 requests13
(10-‐32)
(10-‐34)
► Full autosomal monosomies are not (weeks)
• (10-‐34)
Outgoing and
incoming phone calls
generally compatible
with life; (10-‐25)
as reviewed however, partial and mosaic forms of autosomal monosomy have
29
25
26
81
Outcomes Received
(43.9%)
(71.4%)
(70.3%)
(58.7%)
►
Data
on
138
samples
was reviewed
been reported in liveborns
into one of three categories
Summary ►ofResults
Findings
were classified into one of three categories
2
1
Multiple Aneuploidy
mosaic trisomy 18
Figure 2
 
CONCORDANT
Conclusions
Conclusions
CVS
Y
CBC
p
ocytic
NIPSAutosomal
results relate
to a
Monosomy
single trisomy,• Clinical
other hx:
results
• Clinical hx: 33 y.o. with cystic
23 y.o.may
with be reported.
2
3
I
Su
►
►
►
►
►
OTHER
OTHER
1
OTHER
hygroma and encephalocele
• Clinical hx: 33 y.o.
with►cystic
Single Trisomy
WeMultiple
anticipate that a portion of multiple aneuploidy and
on ultrasound
Single
hygroma and encephalocele
unilateral multicystic
with Sex
Concordance
Total Cohort findings reflect the fetal karyotype
hygroma
and
encephalocele
• NIPS
result: full/partial
Autosomal
Aneuploidy monosomy
Chromosome autosomal
on ultrasound
kidney on ultrasound
Monosomy Abnormality
monosomy
for chromosome
while some may►
be explained
by other etiologies,
such
as
We anticipate
that
a
portion
of
multiple
aneuploidy
and
on ultrasound
• NIPS result: full/partial
• NIPS result: aneuploidy
13
other
maternal/fetal
chromosomal
aberrations,
maternal
5
Concordant
2
1
for chromosome
detected forfindings
chromosomes
• NIPS
result: 2full/partial
autosomal monosomy
reflect themonosomy
fetal karyotype
• Prenatal
dx: declined
disease,
mosaicism
or
co-twin
demise.
13
21
and
13;
full/partial
Concordant
0 chromosome
10
7
3
•Partially
Outcome:
TOP 1secondary
to
monosomy
for
while some may
be explained
by other etiologies,
such as
• Prenatal dx: declined
monosomy
for
ultrasound findings; POC
Discordant
20
44
10 ► Continued
14
•
Outcome:
TOP
secondary to
13
chromosome
18
evaluationother
of outcomes
for complex
NIPS
results
maternal/fetal
chromosomal
aberrations, maternal
karyotype analysis not
ultrasound findings; POC
• Prenatal
diagnosis:
is warranted
to better
understand the biological
reasons
for CVS
2
• Other
Prenatal
dx: 7declined6
22
9
successful
disease,
mosaicism
or
co-twin
demise.
karyotype analysis not
and
Amnio
c/w
46,XY
such results
• Paternal
karyotype: TOP
c/w
• Outcome:
secondary
to10
Outcome
Unknown
successful
25
42
7
• Outcome: Maternal CBC
46,XY t(13;20)(q22:q31.1)
•
Paternal karyotype: c/w
and additional work-up
ultrasound
findings; POC
Outcome
Unknown,
12
15
3
0
►
Continued
evaluation
of
outcomes
for
complex
NIPS results
46,XY t(13;20)(q22:q31.1)
revealed acute lymphocytic
EDD Not Passed3
karyotype analysis not
leukemia (ALL)
OTHER
CVS
Y
CBC
up
hocytic
2
Co
► Although in most cases, abnormal NIPS results relate to a
Autosomal Monosomy single trisomy, other
in reported.
most
cases,
abnormal
results may be
► Although
Multiple
Aneuploidy
Outcomes
• Clinical hx: 33 y.o. with cystic
th
1
placental analysis c/w
mosaic trisomy 18
9.3Mb deletion on
chromosome 13q
Autosomal Monosomy
ith
dy
omes
17
(12.3%)
CONCORDANT
CONCORDANT
ith
al
idy
omes
1
(2.7%)
► Overall, full or partial concordance was confirmed in 15
(10.9%) cases
CONCORDANT
my
d
ery
2
4
(11.4%)
• Clinical hx: 33 y.o. with
Summary of Findings
echogenic intracardiac
► An additional
13Examples
(9.4%) cases were explained by other
Figurefocus
1 and shortened long
Case
concordanceetiologies,
was confirmedincluding
in 15
► Overall, full or partialbiological
maternal malignancy (7,
Multiple Aneuploidy
bones on ultrasound
(10.9%) cases
Result Classification
5.1%), maternal
karyotype
anomalies (1,Multiple
0.7%)Aneuploidy
or other
Autosomal
Monosomy
• Clinical hx: 33 y.o. with
•
NIPS
result:
aneuploidy
n=138
echogenic intracardiac
► An additional 13 (9.4%)
cases
were explained
by hx:
other
fetal
karyotype
anomalies
(5,with
3.6%)
• Clinical hx: 33 y.o. with
• Clinical
24 y.o.
forlong
chromosomes
focusdetected
and shortened
biological etiologies, including maternal malignancy
(7,
echogenic intracardiac
Dandy Walker
bones21
on and
ultrasound
18
focus and shortened long
5.1%), maternal karyotype anomalies (1, malformation
0.7%) or otheron
• NIPS result:
26.8% aneuploidy
►
bones onby
ultrasound
Some
autosomal
monosomies
were
explained
ultrasound
•
Prenatal
dx:
declined
fetal
karyotype
anomalies
Single
Autosomal
Monosomy
(21, 18, 13)(5, 3.6%)
detected for chromosomes
• NIPS result: aneuploidy
47.8%
• NIPS result: full/partial
21 and
18
• Outcome:
postnatal fetal
abnormalities inmonosomy
one of for
the reference chromosomes
used to
Single Trisomy with Sex Chromosome
detected for chromosomes
25.4%
►Abnormality
Some autosomal monosomies were explained
by
• Prenatal
dx:
declined
karyotype c/w 47,+21;
21 and 18
chromosome 13
analyze test chromosomes
• Outcome: postnatal fetal
abnormalities
in one of the reference chromosomes used to
Multiple
Aneuploidy
•
Prenatal dx: declined
•
Prenatal
dx:
declined
placental
analysis c/w analyze test chromosomes
karyotype
c/w 47,+21;
• Outcome: postnatal fetal
• Outcome: term delivery
placental
analysis
c/w
mosaic
trisomy
18
karyotype c/w 47,+21;
• Postnatal array: c/w
th
al
12
EDD not yet passed
► This study evaluates outcomes of clinical
(18.2%)
laboratory noninvasive
prenatal screening (NIPS) samples from singleton pregnancies
Includes AD and AS results
receiving multiple aneuploidy and/orEDD
autosomal
monosomy
results
not passed at time
of data collection
my
d
ery
Re
►
Total
66
138 is warranted to better understand the biological reasons for
35
37
successful
Concordance confirmed for one aneuploidy
such results
• Paternal
karyotype:
c/w
Other outcomes
include SAB/TOP/IUFD,
maternal conditions
and other reported fetal karyotype anomalies
EDD not passed as of data collection
46,XY t(13;20)(q22:q31.1)
References
um Reprod Sci. 2014 Oct-Dec; 7(4): 262–268. doi: 10.4103/0974-1208.147494
A(1):24-32.
1
Subramaniyam S, Pulijaal VR, Matthew S. Double and multiple chromosomal aneuploidies in spontaneous abortions: A single institutional experience. J Hum Reprod Sci. 2014 Oct-Dec; 7(4): 262–268. doi: 10.4103/0974-1208.1474
2
Kovaleva
NV,Mutton
DE.7(4):
Epidemiology
of double
involving chromosome 21 and the sex chromosomes. Am J Med Genet A. 2005 Apr 1;134A(1):24-32.
Sci. 2014
Oct-Dec;
262–268.
doi: aneuploidies
10.4103/0974-1208.147494
1
2
Subramaniyam S, Pulijaal VR, Matthew S. Double and multiple chromosomal aneuploidies in spontaneous abortions: A single institutional experience. J Hum Reprod
Kovaleva NV,Mutton DE. Epidemiology of double aneuploidies involving chromosome 21 and the sex chromosomes. Am J Med Genet A. 2005 Apr 1;134A(1):24-32.
um Reprod Sci. 2014 Oct-Dec; 7(4): 262–268. doi: 10.4103/0974-1208.147494
(1):24-32.