Outcome Following Autosomal Monosomy and Multiple Aneuploidy Results by Noninvasive Prenatal Screening

Holly Snyder, Patricia Devers, Patricia Taneja, Sucheta Bhatt Illumina, Redwood City, CA, USA

Introduction Method Results

► A recent study of cytogenetic analysis following spontaneous ► Database query for all singleton NIPS samples during the study Sample Demographics by Result Classification miscarriage showed that 5% of samples were affected with a period with one of the following results: Single Single Trisomy multiple aneuploidy.1 – Single autosomal monosomy Multiple Autosomal with Sex Aneuploidy1 – Multiple aneuploidy with aneuploidy detected (AD) and/or Monosomy Chromosome Total Abnormality1 ► An estimated 0.16% of trisomy 21 cases involve a double aneuploidy suspected (AS) for chromosomes 21,18,13, X and Y Cases 66 35 37 138 aneuploidy with either XXX, XXY, XYY or MX. The combination of Outcome Following Autosomal Monosomy and Multiple Aneuploidy 2 ► Down syndrome and Klinefelter syndrome is the most common. Outcome information was requested for all cases via: Mean Maternal Age 34.4 37.3 35.3 35.4 • Fax requests OutcomeResults Following by Noninvasive(years) Autosomal Prenatal(19-‐46) ScreeningMonosomy(24-‐47) (23-‐44) (19- and‐47) Multiple Aneuploidy

► Full autosomal monosomies are not generally compatible with life; • Outgoing and incoming phone calls ResultsMean byGestational Noninvasive Age 14.8 12.0 Prenatal14.0 13 Screening however, partial and mosaic forms of autosomal monosomy have Holly Snyder, Patricia Devers,(weeks) Patricia Taneja,(10-‐32) Sucheta(10-‐25) Bhatt(10-‐34) (10-‐34) been reported in liveborns ► Data on 138 samples was reviewed Illumina, Redwood City, CA, USA Holly Snyder, Patricia29 Devers,25 Patricia Taneja,26 Sucheta81 Bhatt Outcomes Received Illumina,(43.9%) Redwood(71.4%) City, CA,(70.3%) USA (58.7%) ► This study evaluates outcomes of clinical laboratory noninvasive ► Results were classified into one of three categories 12 4 1 17 EDD not yet passed2 prenatal screening (NIPS) samples from singleton pregnancies (18.2%) (11.4%) (2.7%) (12.3%) Introduction Method Results receiving multiple aneuploidy and/or autosomal monosomy results 1 ► A recent study of cytogenetic analysis following spontaneousIncludes AD and AS► resultsDatabase query for all singleton NIPS samples during the study Sample Demographics by Result Classification 2 EDD not passed at time of data collection miscarriage showed that 5% of samples were affected with a period with one of the following results: Single Single Trisomy multiple aneuploidy.1 – Single autosomal monosomy Multiple Autosomal with Sex Aneuploidy1 – Multiple aneuploidy with aneuploidy detected (AD) and/or Monosomy Chromosome Total Abnormality1 ► An estimated 0.16% of trisomy 21 cases involve a double aneuploidy suspected (AS) for chromosomes 21,18,13, X and Y Cases 66 35 37 138 aneuploidy with either XXX, XXY, XYY or MX. The combination of Figure 1 Case Examples Summary2 ► of Findings Down syndrome and Klinefelter syndrome is the most common. Outcome information was requested for all cases via: Mean Maternal Age 34.4 37.3 35.3 35.4 • Fax requests (years) (19-‐46) (24-‐47) (23-‐44) (19-‐47)

► Full autosomal monosomies are not generally compatible with life; • Outgoing and incoming phone calls ► Overall, full or partial concordance was confirmed in 15 Mean Gestational Age 14.8 12.0 14.0 13 Result Classification Autosomal Monosomy however,Multiple partial and Aneuploidy mosaic forms of autosomal monosomy have (weeks) (10-‐32) (10-‐25) (10-‐34) (10-‐34) n=138 been reported in liveborns (10.9%) cases► Data on 138 samples was reviewed 29 25 26 81 • Clinical hx: 33 y.o. with Outcomes Received • Clinical hx: 24 y.o. with (43.9%) (71.4%) (70.3%) (58.7%) Dandy Walker ► This study echogenic evaluates outcomes intracardiac of clinical laboratory noninvasive ► Results were classified into one of three categories ► An additional 13 (9.4%) cases were explained by other 12 4 1 17 EDD not yet passed2 malformation on prenatal focus screening and (NIPS) shortened samples fromlong singleton pregnancies (18.2%) (11.4%) (2.7%) (12.3%) 26.8% receiving multiple aneuploidy and/or autosomal monosomy results biological etiologies, including maternal malignancy (7, bones on ultrasound 1 Single Autosomal Monosomy (21, 18, 13) ultrasound Includes AD and AS results 5.1%), maternal karyotype anomalies (1, 0.7%) or other 2 EDD not passed at time of data collection 47.8% • NIPS result: full/partial • NIPS result: aneuploidy Single Trisomy with Sex Chromosome fetal karyotype anomalies (5, 3.6%) 25.4% Abnormality monosomy for detected for chromosomes chromosome 13 21 and 18 Multiple Aneuploidy • Prenatal dx: declined Figure• 1Prenatal dx: declined ► Some autosomalCase Examples monosomies were explained by Summary of Findings

CONCORDANT • Outcome: term delivery • Outcome: postnatal fetal abnormalities in one of the reference chromosomes used to ► Overall, full or partial concordance was confirmed in 15 CONCORDANT Result Classification Autosomal Monosomy Multiple Aneuploidy • Postnatal array: c/w karyotype c/w 47,+21;n=138 analyze test chromosomes (10.9%) cases 9.3Mb deletion on placental analysis c/w • Clinical hx: 24 y.o. with • Clinical hx: 33 y.o. with Dandy Walker echogenic intracardiac ► An additional 13 (9.4%) cases were explained by other chromosome 13q mosaic trisomy 18 malformation on focus and shortened long biological etiologies, including maternal malignancy (7, 26.8% ultrasound bones on ultrasound Single Autosomal Monosomy (21, 18, 13) 5.1%), maternal karyotype anomalies (1, 0.7%) or other 47.8% • NIPS result: full/partial • NIPS result: aneuploidy Single Trisomy with Sex Chromosome monosomy for detected for chromosomes fetal karyotype anomalies (5, 3.6%) Figure 2 25.4% Abnormality Conclusions chromosome 13 21 and 18 Multiple Aneuploidy • Prenatal dx: declined • Prenatal dx: declined ► Some autosomal monosomies were explained by

CONCORDANT • Outcome: term delivery • Outcome: postnatal fetal abnormalities in one of the reference chromosomes used to Outcomes Multiple Aneuploidy Autosomal Monosomy ► Although in most cases, abnormal NIPSCONCORDANT results relate to a • Postnatal array: c/w karyotype c/w 47,+21; analyze test chromosomes • Clinical hx: 23 y.o. with • Clinical hx: 33 y.o. with cystic single trisomy, 9.3Mb other deletion results on may be reported. placental analysis c/w Single Trisomy chromosome 13q mosaic trisomy 18 Single Multiple with Sex unilateral multicystic hygroma and encephalocele Concordance Autosomal Aneuploidy Total Cohort Chromosome kidney on ultrasound on ultrasound ► We anticipate that a portion of multiple aneuploidy and Monosomy Abnormality Figure 2 Conclusions • NIPS result: aneuploidy • NIPS result: full/partial autosomal monosomy findings reflect the fetal karyotype

Concordant 2 2 1 5 detected for chromosomes monosomy forOutcomes chromosome while some mayMultiple be Aneuploidy explained by otherAutosomal etiologies, Monosomy such as ► Although in most cases, abnormal NIPS results relate to a • Clinical hx: 23 y.o. with • Clinical hx: 33 y.o. with cystic single trisomy, other results may be reported. 1 21 and 13; full/partial 13 Single Trisomy Partially Concordant 0 7 3 10 Single Multiple other maternal/fetal chromosomal aberrations, maternal with Sex unilateral multicystic hygroma and encephalocele Concordance• PrenatalAutosomal dx: declined Aneuploidy Total Cohort monosomy for Chromosome disease, mosaicism kidney on orultrasound co-twin demise. on ultrasound ► We anticipate that a portion of multiple aneuploidy and Monosomy Abnormality OTHER Discordant 20 10 14 44 chromosome 18 OTHER • Outcome: TOP secondary to • NIPS result: aneuploidy • NIPS result: full/partial autosomal monosomy findings reflect the fetal karyotype • Prenatal diagnosis: CVS Concordant ultrasound 2findings;2 POC 1 5 detected for chromosomes monosomy for chromosome while some may be explained by other etiologies, such as Other2 7 6 9 22 13 1 ► Continued evaluation 21 and 13; full/partialof outcomes for complex NIPS results other maternal/fetal chromosomal aberrations, maternal and Amnio c/w 46,XY Partially Concordant karyotype analysis0 7not 3 10 is warranted tomonosomy better forunderstand the biological• Prenatal dx: reasonsdeclined for disease, mosaicism or co-twin demise. OTHER Outcome Unknown 25 7 10 42 • Outcome: Maternal CBC Discordant successful20 10 14 44 chromosome 18 OTHER • Outcome: TOP secondary to • Prenatal diagnosis: CVS ultrasound findings; POC and additional work-up Other• Paternal2 karyotype:7 6 c/w 9 22 such results ► Continued evaluation of outcomes for complex NIPS results Outcome Unknown, and Amnio c/w 46,XY karyotype analysis not 12 3 0 15 is warranted to better understand the biological reasons for EDD Not Passed3 revealed acute lymphocytic Outcome 46,XYUnknown t(13;20)(q22:q31.1)25 7 10 42 • Outcome: Maternal CBC successful and additional work-up • Paternal karyotype: c/w such results leukemia (ALL) Outcome Unknown, 12 3 0 15 Total 66 35 37 138 EDD Not Passed3 revealed acute lymphocytic 46,XY t(13;20)(q22:q31.1) leukemia (ALL) 66 35 37 138 1 Concordance confirmed for one aneuploidy Total 2 Other outcomes include SAB/TOP/IUFD, maternal conditions and other reported fetal karyotype anomalies 1 Concordance confirmed for one aneuploidy 3EDD not passed as of data collection 2Other outcomes include SAB/TOP/IUFD, maternal conditions and other reported fetal karyotype anomalies 3EDD not passed as of data collection

References 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 1 Subramaniyam S, Pulijaal VR, Matthew S. Double and multiple chromosomal aneuploidies in spontaneous abortions: A single institutional experience. J Hum Reprod 2 Sci.Kovaleva 2014 NV,Mutton Oct-Dec; DE. Epidemiology 7(4): 262–268. of double doi: aneuploidies 10.4103/0974-1208.147494 involving chromosome 21 and the sex chromosomes. Am J Med Genet A. 2005 Apr 1;134A(1):24-32.

2 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. Outcome Following Autosomal Monosomy and Multiple Aneuploidy Results by Noninvasive Prenatal Screening

Holly Snyder, Patricia Devers, Patricia Taneja, Sucheta Bhatt Illumina, Redwood City, CA, USA

Introduction Method Results

► A recent study of cytogenetic analysis following spontaneous ► Database query for all singleton NIPS samples during the study Sample Demographics by Result Classification miscarriage showed that 5% of samples were affected with a period with one of the following results: Outcome Following Autosomal Monosomy and Multiple Aneuploidy Single Trisomy 1 Single multiple aneuploidy. – Single autosomal monosomy with Sex Multiple Outcome Following AutosomalAutosomal Monosomy1 and Multiple Aneuploidy Aneuploidy Results by – Multiple Noninvasive aneuploidy with aneuploidy Prenatal detected (AD) and/orScreening Monosomy Chromosome Total Abnormality1 ► An estimated 0.16% of trisomy 21 cases involve a double aneuploidy suspected (AS) for chromosomes 21,18,13, X andResults Y by Noninvasive Prenatal Screening aneuploidy with either XXX, XXY, XYY or MX. The combination of Holly Snyder, Patricia Devers, Patricia Taneja, Sucheta Bhatt Cases 66 35 37 138 Illumina, Redwood City, CA, USA Down syndrome and Klinefelter syndrome is the most common.2 ► Outcome information was requested for all cases via: Holly Snyder, Patricia Devers, Patricia Taneja, Sucheta Bhatt Mean Maternal Age Illumina,34.4 Redwood37.3 City, CA,35.3 USA 35.4 • Fax requests (years) (19-‐46) (24-‐47) (23-‐44) (19-‐47)

► • Outgoing and incoming phone calls Full autosomal monosomiesIntroduction are not generally compatible with life; Method Results Mean Gestational Age 14.8 12.0 14.0 13 however, partial and mosaic forms of autosomal monosomy have Introduction (weeks) Method(10-‐32) (10-‐25) (10-‐34) (10-‐34) Results Sample Demographics by Result Classification been reported in liveborns► A recent study of cytogenetic analysis following spontaneous ► Data► on Database 138 samples query for all was singleton reviewed NIPS samples during the study miscarriage showed that 5% of samples were affected with a period with one of the following results: ► A recent study of cytogenetic analysis following spontaneous Single Trisomy► Database29 query for all singleton25 NIPS samples26 during the81 study Sample Demographics by Result Classification 1 OutcomesSingle Received multiple aneuploidy. – Single autosomal monosomy Multiple miscarriage showed that 5% of samples were affected withAutosomal a with Sex period(43.9%) with one of the (71.4%)following results:(70.3%) (58.7%) Chromosome Aneuploidy1 Total Single Trisomy – Multiple aneuploidy with aneuploidy detected (AD) and/or1 Monosomy Single ► ► multiple aneuploidy. 1 – Single autosomal monosomy Multiple This study evaluates outcomes of clinical laboratory noninvasive Results were classified into one of three categories Abnormality Autosomal with Sex ► An estimated 0.16% of trisomy 21 cases involve a double aneuploidy suspected (AS) for chromosomes 21,18,13, X and Y Chromosome Aneuploidy1 Total 2 – Multiple12 aneuploidy with4 aneuploidy detected1 (AD) and/or17 Monosomy prenatal screening (NIPS) samples from singleton pregnancies Cases EDD66 not yet passed35 37 138 Abnormality1 aneuploidy with either XXX, XXY, XYY or MX. The combination of ► An estimated 0.16% of trisomy 21 cases involve a double aneuploidy(18.2%) suspected(11.4%) (AS) for chromosomes(2.7%) 21,18,13,(12.3%) X and Y 2 receiving multiple aneuploidyDown and/or syndrome autosomal and Klinefelter monosomy syndrome isresults the most common. ► Outcome information was requested for all cases via: Cases 66 35 37 138 aneuploidy with either XXX, XXY, XYYMean or Maternal MX. The Age combination34.4 of 37.3 35.3 35.4 • Fax requests (years) 1 Includes(19-‐46) AD2 and(24- AS‐47) results (23-‐44) (19-‐47) Down syndrome and Klinefelter syndrome is the most common. ► Outcome information was requested for all cases via: Mean Maternal Age ► Full autosomal monosomies are not generally compatible with life; • Outgoing and incoming phone calls 2 EDD not passed at time of data collection 34.4 37.3 35.3 35.4 Mean Gestational Age 14.8 12.0 • Fax14.0 requests13 (years) (19-‐46) (24-‐47) (23-‐44) (19-‐47) however, partial and mosaic forms of autosomal monosomy have ► Full autosomal monosomies are not (weeks)generally compatible(10- with‐32) life; (10-‐25) • (10-Outgoing‐34) and(10-‐ 34)incoming phone calls been reported in liveborns ► Data on 138 samples was reviewed Mean Gestational Age 14.8 12.0 14.0 13 however, partial and mosaic forms of autosomal monosomy29 have 25 26 81 (weeks) (10-‐32) (10-‐25) (10-‐34) (10-‐34) Outcomes Received been reported in liveborns (43.9%) (71.4%)► Data(70.3%) on 138 samples(58.7%) was reviewed 29 25 26 81 ► This study evaluates outcomes of clinical laboratory noninvasive ► Results were classified into one of three categories Outcomes Received 12 4 1 17 (43.9%) (71.4%) (70.3%) (58.7%) EDD not yet passed2 Figure 1 prenatal screening (NIPS) samples from singleton pregnanciesCase Examples ► This study evaluates outcomes of clinical laboratorySummary noninvasive(18.2%) (11.4%) ►ofResults (2.7%)Findings were(12.3%) classified into one of three categories 12 4 1 17 receiving multiple aneuploidy and/or autosomal monosomy results EDD not yet passed2 prenatal screening (NIPS) samples from singleton pregnancies (18.2%) (11.4%) (2.7%) (12.3%) 1 Includes AD and AS results receiving multiple aneuploidy and/or2 EDD autosomal not passed at timemonosomy of data collection results ► Overall, full or partial concordance was confirmed in 15 1 Result Classification Includes AD and AS results Autosomal Monosomy Multiple Aneuploidy 2 EDD not passed at time of data collection n=138 (10.9%) cases • Clinical hx: 24 y.o. with • Clinical hx: 33 y.o. with Figure 1 Case Examples Summary of Findings Dandy Walker echogenic intracardiac Figure 1 ► An additionalCase 13 Examples (9.4%) cases were explained by other Summary of Findings malformation on focus and shortened long► Overall, full or partial concordance was confirmed in 15 Result Classification Autosomal Monosomy Multiple Aneuploidy biological etiologies, including maternal malignancy (7, 26.8% bones on ultrasound (10.9%) cases Single Autosomal Monosomyn=138 (21, 18, 13) ultrasound ► Overall, full or partial concordance was confirmed in 15 • Clinical hx: 24 y.o. with • Clinical hx: 33 y.o. withResult Classification 5.1%), maternalAutosomal karyotype Monosomy anomalies (1,Multiple 0.7%) Aneuploidy or other 47.8% • NIPS result: aneuploidy (10.9%) cases • NIPS result:Dandy Walker full/partial echogenic intracardiac n=138 Single Trisomy with Sex Chromosome ► An additional 13 (9.4%)fetal cases karyotype were explained• Clinicalanomalies by hx:other 24 y.o.(5, with 3.6%) • Clinical hx: 33 y.o. with monosomy malformation for on focus detected and shortened for long chromosomes 25.4% Abnormality biological etiologies, including maternal malignancy Dandy Walker (7, echogenic intracardiac 26.8% ultrasound bones on ultrasound ► An additional 13 (9.4%) cases were explained by other Single Autosomal Monosomy (21, 18, 13) chromosome 13 21 and 18 5.1%), maternal karyotype anomalies (1, malformation0.7%) or other on focus and shortened long Multiple 47.8%Aneuploidy • NIPS result: full/partial • NIPS result:26.8% aneuploidy biological etiologies, including maternal malignancy (7, Single Trisomy with Sex Chromosome ► Some autosomal ultrasound monosomies were explained bones on by ultrasound • Prenatal monosomy dx: declined for detected• Prenatal for chromosomes dx: declined Singlefetal Autosomal karyotype Monosomy anomalies (21, 18, 13) (5, 3.6%) 5.1%), maternal karyotype anomalies (1, 0.7%) or other 25.4% Abnormality 47.8% • NIPS result: full/partial • NIPS result: aneuploidy chromosome 13 21 and 18 Single Trisomy with Sex Chromosome CONCORDANT • Outcome: term delivery • Outcome: postnatal fetal abnormalities in one of the reference chromosomes used to fetal karyotype anomalies (5, 3.6%) Multiple Aneuploidy monosomy for detected for chromosomes

CONCORDANT 25.4% • Prenatal dx: declined • Prenatal dx: declined ►AbnormalitySome autosomal monosomies were explained by • Postnatal array: c/w karyotype c/w 47,+21; analyze test chromosomes chromosome 13 21 and 18 CONCORDANT • Outcome: term delivery • Outcome: postnatal fetal Multipleabnormalities Aneuploidy in one of the reference chromosomes used to ► CONCORDANT • Prenatal dx: declined • Prenatal dx: declined Some autosomal monosomies were explained by 9.3Mb• Postnataldeletion array: on c/w karyotype placental c/w 47,+21; analysis c/w analyze test chromosomes

CONCORDANT • Outcome: term delivery • Outcome: postnatal fetal abnormalities in one of the reference chromosomes used to

9.3Mb deletion on placental analysis c/w CONCORDANT chromosome 13q mosaic trisomy 18 • Postnatal array: c/w karyotype c/w 47,+21; analyze test chromosomes chromosome 13q mosaic trisomy 18 9.3Mb deletion on placental analysis c/w chromosome 13q mosaic trisomy 18 Figure 2 Figure 2 ConclusionsConclusions

Figure 2 Conclusions Outcomes Multiple Aneuploidy Autosomal Monosomy ► Although in most cases, abnormal NIPS results relate to a Autosomal Monosomy Outcomes Multiple Aneuploidy • Clinical hx: 33 y.o. with cysticOutcomes single trisomy, other► Althoughresults may bein reported.mostMultiple cases, Aneuploidy abnormal NIPSAutosomal results relate Monosomy to a Single Trisomy • Clinical hx: 23 y.o. with ► Although in most cases, abnormal NIPS results relate to a Single Multiple with Sex unilateral multicystic hygroma and encephalocele single trisomy, other results may be reported. Concordance Autosomal Aneuploidy Total Cohort single trisomy,• Clinicalother hx:results 23 y.o. may with be reported.• Clinical hx: 33 y.o. with cystic Chromosome • Clinical hx: 23 y.o. with • Clinical hx: 33 y.o.Single with Trisomy► cysticWe anticipate that a portion of multiple aneuploidy and Single Trisomy Monosomy kidney on ultrasound on ultrasound Single Multiple Single Multiple Abnormality with Sex unilateral multicystic hygroma and encephalocele with Sex unilateral• NIPS multicystic result: aneuploidy • NIPSConcordance hygroma result: full/partial andAutosomal encephaloceleautosomalAneuploidy monosomyTotal Cohort findings reflect the fetal karyotype Concordance Total Cohort Chromosome kidney on ultrasound on ultrasound ► We anticipate that a portion of multiple aneuploidy and Autosomal ChromosomeConcordant Aneuploidy2 2 1 5 detected for chromosomes monosomy for chromosomeMonosomy Abnormality kidney on ultrasound on ultrasound while some may► be explainedWe anticipate by other etiologies, •that NIPS a result: portion such aneuploidy as of multiple aneuploidy• NIPS result: full/partial and autosomal monosomy findings reflect the fetal karyotype Monosomy Abnormality 21 and 13; full/partial 13 Partially Concordant1 0 7 3 10 Concordant 2 2 other 1maternal/fetal5 chromosomal aberrations, detected maternal for chromosomes monosomy for chromosome • NIPS result: aneuploidy • Prenatal• NIPS dx: declinedresult: full/partial autosomal monosomy findings reflect the fetal karyotype while some may be explained by other etiologies, such as monosomy for disease, mosaicism or co-twin demise. 13 1 21 and 13; full/partial other maternal/fetal chromosomal aberrations, maternal OTHER Concordant 2 Discordant2 201 10 5 14 44 detected chromosome for chromosomes 18 OTHER •Partially Outcome: monosomy Concordant TOP secondary for0 chromosome to 7 3 10 while some may be explained by other etiologies, such as monosomy for • Prenatal dx: declined disease, mosaicism or co-twin demise. 2 • Prenatal diagnosis: CVS ultrasound findings; POC OTHER Other 7 6 9 22 21 and 13; full/partial Discordant 13 20 10 ► Continued14 evaluation44 of outcomes for complex chromosome NIPS results 18 OTHER • Outcome: TOP secondary to Partially Concordant1 0 7 3 10 and Amnio c/w 46,XY karyotype analysis not other maternal/fetal chromosomal aberrations, maternal 2 is warranted to better understand the biological• Prenatal reasons diagnosis: for CVS ultrasound findings; POC Outcome Unknown 25 7 10 42 monosomy• Outcome: for Maternal CBC successful• OtherPrenatal dx: 7declined6 9 22 ► Continued evaluation of outcomes for complex NIPS results disease, mosaicism and Amnio or co-twinc/w 46,XY demise. karyotype analysis not • Paternal karyotype: c/w such results OTHER and additional work-up is warranted to better understand the biological reasons for Discordant 20 Outcome10 Unknown, 14 44 OTHER Outcome• Outcome: Unknown TOP25 secondary7 to10 42 12 3 0 15 chromosome 18 • Outcome: Maternal CBC successful 3 revealed acute lymphocytic 46,XY t(13;20)(q22:q31.1) EDD Not Passed and additional work-up • Paternal karyotype: c/w such results • Prenatal diagnosis: CVS Outcome ultrasound Unknown, findings; POC Other2 leukemia (ALL) 12 3 0 15 7 Total6 669 35 22 37 138 EDD Not Passed3 ► Continued evaluation revealed acuteof outcomes lymphocytic for complex 46,XY t(13;20)(q22:q31.1) NIPS results and Amnio c/w 46,XY karyotype analysis not leukemia (ALL) 1 Concordance confirmed for one aneuploidy Total 66 35 37 138 is warranted to better understand the biological reasons for 2 Outcome Unknown 25 Other outcomes7 include SAB/TOP/IUFD,10 maternal conditions and 42other reported fetal karyotype anomalies • Outcome: Maternal CBC successful 3EDD not passed as of data collection 1 Concordance confirmed for one aneuploidy such results and additional work-up 2Other outcomes• Paternal include SAB/TOP/IUFD, karyotype: maternal conditions c/w and other reported fetal karyotype anomalies Outcome Unknown, 3 12 3 0 15 EDD not passed as of data collection EDD Not Passed3 revealed acute lymphocytic 46,XY t(13;20)(q22:q31.1) leukemia (ALL) Total 66 References35 37 138

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 1 Concordance confirmed for one aneuploidy References 2 2 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. 1 Other outcomes include SAB/TOP/IUFD, maternal conditions and other reported fetal karyotype anomalies 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 3EDD not passed as of data collection Subramaniyam S, Pulijaal VR, Matthew S. Double and multiple chromosomal aneuploidies in spontaneous abortions: A single institutional experience. J Hum Reprod 2 KovalevaSci. 2014 NV,Mutton Oct-Dec; DE. 7(4):Epidemiology 262–268. of double doi: aneuploidies10.4103/0974-1208.147494 involving chromosome 21 and the sex chromosomes. Am J Med Genet A. 2005 Apr 1;134A(1):24-32.

2 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.

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

2 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.