Risk of Clinically Significant Chromosomal Microarray Analysis Findings in Fetuses With Nuchal Translucency From 3.0 mm Through 3.4 mm

Abstract Background This study aimed to evaluate the applicability of chromosomal microarray analysis (CMA) for prenatal diagnosis of craniofacial malformations (CFMs). We also investigated the potential correlations between chromosomal abnormalities and CFMs. To this end, 118 fetuses with CFMs were enrolled in the study and underwent both G-banded chromosome analysis and CMA. Results Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities or submicroscopic chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic CNVs only (10/118; 8.5%). We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes. Conclusion CMA is a rapid and reliable molecular technique to identify fetal chromosomal aberrations associated with CFMs. Identification of the genetic basis of CFMs contributes to the understanding of their pathogenesis and etiology.

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Chromosomal Microarray Analysis versus Karyotyping in Fetuses with Increased Nuchal Translucency

Medical Sciences ◽

10.3390/medsci7030040 ◽

2019 ◽

Vol 7 (3) ◽

pp. 40 ◽

Cited By ~ 1

Author(s):

Rita Cicatiello ◽

Piero Pignataro ◽

Antonella Izzo ◽

Nunzia Mollo ◽

Lucia Pezone ◽

...

Keyword(s):

Microarray Analysis ◽

Chromosomal Rearrangements ◽

Prenatal Testing ◽

Normal Karyotype ◽

Nuchal Translucency ◽

Cystic Hygroma ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Chromosomal Anomalies ◽

Increased Nuchal Translucency

We have carried out a retrospective study of chromosome anomalies associated with increased nuchal translucency (NT) in order to compare yield rates of karyotype, chromosome microarray analysis (CMA), and non-invasive prenatal testing (NIPT) in this condition. Presenting with increased NT or cystic hygroma ≥3.5 mm as an isolated sign, 249 fetuses underwent karyotype and/or CMA from 11 to 18 gestational weeks. Karyotype and fluorescence in situ hybridization (FISH) analyses detected 103 chromosomal anomalies including 95 aneuploidies and eight chromosomal rearrangements or derivatives. Further, seven pathogenic copy number variants (CNV), five likely pathogenic CNVs, and 15 variants of unknown significance (VOUS) were detected by CMA in fetuses with normal karyotype. Genetic testing is now facing new challenges due to results with uncertain clinical impacts. Additional investigations will be necessary to interpret these findings. More than 15% of the anomalies that we have diagnosed with invasive techniques could not be detected by NIPT. It is therefore definitely not recommended in the case of ultrasound anomalies. These results, while corroborating the use of CMA in fetuses with increased NT as a second tier after rapid aneuploidy testing, do not suggest a dismissal of karyotype analysis.

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Clinical application of chromosomal microarray analysis in fetuses with increased nuchal translucency and normal karyotype

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.811 ◽

2019 ◽

Vol 7 (8) ◽

Cited By ~ 1

Author(s):

Linjuan Su ◽

Hailong Huang ◽

Gang An ◽

Meiying Cai ◽

Xiaoqing Wu ◽

...

Keyword(s):

Clinical Application ◽

Microarray Analysis ◽

Normal Karyotype ◽

Nuchal Translucency ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Increased Nuchal Translucency

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Prenatal chromosomal microarray analysis of fetus with increased nuchal translucency

Journal of Genetic Medicine ◽

10.5734/jgm.2018.15.2.49 ◽

2018 ◽

Vol 15 (2) ◽

pp. 49-54

Author(s):

So Hyun Shim ◽

Dong Hyun Cha

Keyword(s):

Microarray Analysis ◽

Nuchal Translucency ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Increased Nuchal Translucency

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Chromosomal Microarray Analysis in Pregnancies With Corpus Callosum or Posterior Fossa Anomalies

Neurology Genetics ◽

10.1212/nxg.0000000000000585 ◽

2021 ◽

Vol 7 (3) ◽

pp. e585

Author(s):

Lior Greenbaum ◽

Idit Maya ◽

Lena Sagi-Dain ◽

Rivka Sukenik-Halevy ◽

Michal Berkenstadt ◽

...

Keyword(s):

Corpus Callosum ◽

Posterior Fossa ◽

Microarray Analysis ◽

Detection Rate ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Health Database ◽

Clinically Significant ◽

Normal Ultrasound ◽

Cns Anomalies

ObjectiveWe investigated the detection rate of clinically significant chromosomal microarray analysis (CMA) results in pregnancies with sonographic diagnosis of fetal corpus callosum anomalies (CCA) or posterior fossa anomalies (PFA).MethodsAll CMA tests in pregnancies with CCA or PFA performed between January 2015 and June 2020 were retrospectively evaluated from the Israeli Ministry of Health database. The rate of CMA with clinically significant (pathogenic or likely pathogenic) findings was calculated and compared to a local Israeli cohort of 5,541 pregnancies with normal ultrasound.ResultsOne hundred eighty-two pregnancies were enrolled: 102 cases with CCA and 89 with PFA (9 cases had both). Clinically significant CMA results were found in 7/102 of CCA (6.9%) and in 7/89 of PFA (7.9%) cases. The CMA detection rate in pregnancies with isolated CCA (2/57, 3.5%) or PFA (2/50, 4.0%) was lower than in nonisolated cases, including additional CNS and/or extra-CNS sonographic anomalies (CCA-5/45, 11.1%; PFA-5/39, 12.8%), but this was not statistically significant. However, the rate among pregnancies that had extra-CNS anomalies, with or without additional CNS involvement (CCA-5/24, 20.8%; PFA-5/29, 17.2%), was significantly higher compared to all other cases (p = 0.0075 for CCA; p = 0.035 for PFA). Risk of CMA with clinically significant results for all and nonisolated CCA or PFA pregnancies was higher compared to the background risk reported in the control cohort (p < 0.001), but was not significant for isolated cases.ConclusionsOur findings suggest that CMA testing is beneficial for the genetic workup of pregnancies with CCA or PFA, and is probably most informative when additional extra-CNS anomalies are observed.

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