Increased nuchal translucency with normal karyotype: a follow‐up study of 100 cases supplemented with CGH and MLPA analyses

Schou, Katrine Vasehus; Kirchhoff, Maria; Nygaard, Ulrikka; Jörgensen, Connie; Sundberg, Karin

doi:10.1002/uog.7468

Cited by 33 publications

(41 citation statements)

References 22 publications

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“…These differences in frequencies of chromosomal aberrations in published cohorts were observed before [42] and it may be a consequence of both cohort selection and differences in array design. Many of previously reported cohorts were either retrospectively tested and highly selected [38, 39] or included a heterogeneous group of fetuses with and without additional ultrasound anomalies detected in both first and second trimester [36, 38, 44, 45]. Our results show that the prevalence of submicroscopic aberrations in fetuses with enlarged NT resembles the prevalence in fetuses without ultrasound anomalies.…”

Section: Discussionmentioning

confidence: 61%

“…The incidence of pathogenic submicroscopic chromosomal abnormalities in fetuses with an enlarged NT has been studied by only few groups [36–41] resulting in conflicting conclusions [42, 43]. These differences in frequencies of chromosomal aberrations in published cohorts were observed before [42] and it may be a consequence of both cohort selection and differences in array design.…”

Section: Discussionmentioning

confidence: 99%

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Enlarged NT (≥3.5 mm) in the first trimester – not all chromosome aberrations can be detected by NIPT

et al. 2016

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BackgroundSince non-invasive prenatal testing (NIPT) in maternal blood became available, we evaluated which chromosome aberrations found in our cohort of fetuses with an enlarged NT in the first trimester of pregnancy (tested with SNP microarray) could be detected by NIPT as well.Method362 fetuses were referred for cytogenetic testing due to an enlarged NT (≥3.5 mm). Chromosome aberrations were investigated using QF-PCR, karyotyping and whole genome SNP array.ResultsAfter invasive testing a chromosomal abnormality was detected in 137/362 (38 %) fetuses. 100/362 (28 %) cases concerned trisomy 21, 18 or 13, 25/362 (7 %) an aneuploidy of sex chromosomes and 3/362 (0.8 %) triploidy. In 6/362 (1.6 %) a pathogenic structural unbalanced chromosome aberration was seen and in 3/362 (0.8 %) a susceptibility locus for neurodevelopmental disorders was found. We estimated that in 2–10 % of fetuses with enlarged NT a chromosome aberration would be missed by current NIPT approaches.ConclusionBased on our cohort of fetuses with enlarged NT we may conclude that NIPT, depending on the approach, will miss chromosome aberrations in a significant percentage of pregnancies. Moreover all abnormal NIPT results require confirmatory studies with invasive testing, which will delay definitive diagnosis in ca. 30 % of patients. These figures are important for pretest counseling enabling pregnant women to make informed choices on the prenatal test. Larger cohorts of fetuses with an enlarged NT should be investigated to assess the additional diagnostic value of high resolution array testing for this indication.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Enlarged NT (≥3.5 mm) in the first trimester – not all chromosome aberrations can be detected by NIPT

et al. 2016

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“…While pregnancies found to have increased NT/nuchal fold or cystic hygroma had the highest rate of aneuploidy (30.9%), we did not detect any microdeletions or microduplications in this group. Some reports suggest that this ultrasound abnormality is not associated with an increased risk for submicroscopic chromosome abnormalities [30,[32][33][34] , but other studies have found such abnormalities using microarrays or other molecular tests, including the identification of some of the syndromes on our panel, such as 22q11.21 microdeletions [29,[35][36][37] .…”

Section: Discussionmentioning

confidence: 88%

Experience Using a Rapid Assay for Aneuploidy and Microdeletion/Microduplication Detection in over 2,900 Prenatal Specimens

Sa²,

Hummel³

et al. 2014

Fetal Diagn Ther

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Background: While microarray testing can identify chromosomal abnormalities missed by karyotyping, its prenatal use is often avoided in low-risk pregnancies due to the possible identification of variants of uncertain significance (VOUS). Methods: We tested 2,970 prenatal samples of all referral indications using a rapid BACs-on-Beads-based assay with probes for sex chromosomes, common autosomal aneuploidies, and 20 microdeletion/microduplication syndromes, designed as an alternative to microarray in low-risk pregnancies and an alternative to rapid aneuploidy testing in pregnancies also undergoing microarray analysis. Results: Interpretable results were obtained in 2,940 cases (99.0%), with 89% receiving results in 1 day. Aneuploidies were detected in 7.3% and partial chromosome abnormalities in 0.45% (n = 13), including 5 referred for maternal age, abnormal maternal serum screen, or isolated ultrasound markers. The added detection above karyotype was 1 in 745 in lower-risk cases with normal ultrasounds or isolated ultrasound markers/increased nuchal measurements and 1 in 165 for fetuses with structural/growth abnormalities. Neither false negatives nor false positives were found within test limitations. Female polyploidy could not be detected, while polyploidies with Y chromosomes were suspected and confirmed through additional analysis. Conclusion: When combined with karyotyping, this assay provides increased interrogation of specific chromosomal regions, while limiting VOUS identification.

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“…Roselló et al [2010] investigated the presence of cryptic rearrangements in subtelomeric or microdeletion syndrome regions by MLPA in fetuses with ultrasound abnormalities between the 11th and 13th week of gestation or positive screening in the first trimester and with a normal karyotype, but no chromosomal imbalances were detected in 24 fetuses with increased NT. Schou et al [2009] screened 100 fetuses with NT at or above the 99th percentile, with 10 of them having other sonographic abnormalities, by HR-CGH and subtelomeric and syndrome-specific MLPA. Using this combination, no chromosomal abnormalities were detected.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Screening of 21 Microdeletion/Microduplication Syndromes and Subtelomeric Imbalances by MLPA in Fetuses with Increased Nuchal Translucency and Normal Karyotype

Gouas¹,

Kemeny²,

Beaufrère³

et al. 2015

Cytogenet Genome Res

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Fetuses with increased nuchal translucency thickness (NT) are at increased risk for chromosomal abnormalities. In case of a normal karyotype, a minority of them may present with structural abnormalities or genetic syndromes, which may be related to submicroscopic chromosomal imbalances. The objective of this study was to evaluate whether MLPA screening of 21 syndromic and subtelomeric regions could improve the detection rate of small chromosomal aberrations in fetuses with increased NT and a normal karyotype. A total of 106 prenatal samples from fetuses with NT ≥99th centile and normal R- and G-banding were analyzed by MLPA for subtelomeric imbalances (SALSA P036 and P070) and 21 syndromic regions (SALSA P245). One sample showed a benign CNV (dup(8)pter, FBXO25 gene), and 1 patient was found to have a loss of 18qter and a gain of 5pter as a result of an unbalanced translocation. The incidence of cryptic pathogenic variants was <1% or 2.7% when only fetuses with other ultrasound abnormalities were taken into account. Submicroscopic imbalances in fetuses with increased NT may be individually rare, and genome-wide screening seems more likely to improve the diagnostic yield in these fetuses.

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Increased nuchal translucency with normal karyotype: a follow‐up study of 100 cases supplemented with CGH and MLPA analyses

Abstract: Objective To evaluate whether high-resolution comparative genomic hybridization (HR-CGH)

Cited by 33 publications

References 22 publications

Enlarged NT (≥3.5 mm) in the first trimester – not all chromosome aberrations can be detected by NIPT

Enlarged NT (≥3.5 mm) in the first trimester – not all chromosome aberrations can be detected by NIPT

Experience Using a Rapid Assay for Aneuploidy and Microdeletion/Microduplication Detection in over 2,900 Prenatal Specimens

Prenatal Screening of 21 Microdeletion/Microduplication Syndromes and Subtelomeric Imbalances by MLPA in Fetuses with Increased Nuchal Translucency and Normal Karyotype

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