Chromosomal Microarray in Prenatal Diagnosis: Case Studies and Clinical Challenges

Leavitt, Karla; Goldwaser, Tamar; Bhat, Gifty; Kalia, Isha; Klugman, Susan; Dolan, Siobhan M.

doi:10.2217/pme-2015-0003

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…It has gradually replaced karyotyping in several countries for other indications too [82,[299][300][301]. The detection of submicroscopic CNVs allows the identification of a wider range of causes of malformations [302][303][304][305][306]. It represents a more standardized technique than karyotyping, being less prone to human errors.…”

Section: Chromosomal Microarray Analysismentioning

confidence: 99%

Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges—Systematic Review of the Literature and Meta-Analysis

et al. 2022

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Fetal malformations occur in 2–3% of pregnancies. They require invasive procedures for cytogenetics and molecular testing. “Structural anomalies” include non-transient anatomic alterations. “Soft markers” are often transient minor ultrasound findings. Anomalies not fitting these definitions are categorized as “dynamic”. This meta-analysis aims to evaluate the diagnostic yield and the rates of variants of uncertain significance (VUSs) in fetuses undergoing molecular testing (chromosomal microarray (CMA), exome sequencing (ES), genome sequencing (WGS)) due to ultrasound findings. The CMA diagnostic yield was 2.15% in single soft markers (vs. 0.79% baseline risk), 3.44% in multiple soft markers, 3.66% in single structural anomalies and 8.57% in multiple structural anomalies. Rates for specific subcategories vary significantly. ES showed a diagnostic rate of 19.47%, reaching 27.47% in multiple structural anomalies. WGS data did not allow meta-analysis. In fetal structural anomalies, CMA is a first-tier test, but should be integrated with karyotype and parental segregations. In this class of fetuses, ES presents a very high incremental yield, with a significant VUSs burden, so we encourage its use in selected cases. Soft markers present heterogeneous CMA results from each other, some of them with risks comparable to structural anomalies, and would benefit from molecular analysis. The diagnostic rate of multiple soft markers poses a solid indication to CMA.

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Section: Chromosomal Microarray Analysismentioning

confidence: 99%

Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges—Systematic Review of the Literature and Meta-Analysis

et al. 2022

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“…CMA allows the detection of small rearrangements that can underlie several structural anomalies [ 108 , 109 , 110 , 111 , 112 ]. This technique has largely replaced conventional karyotyping, becoming the first-tier genetic investigation after the detection of fetal structural anomalies in several countries, even if the most used approach (array-comparative genomic hybridization: a-CGH) is not able to identify balanced chromosomal aberrations, triploidies and mosaicisms below 30%.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Microarray Analysis in Fetuses Detected with Isolated Cardiovascular Malformation: A Multicenter Study, Systematic Review of the Literature and Meta-Analysis

et al. 2022

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Cardiovascular malformations (CVM) represent the most common structural anomalies, occurring in 0.7% of live births. The CVM prenatal suspicion should prompt an accurate investigation with fetal echocardiography and the assessment through genetic counseling and testing. In particular, chromosomal microarray analysis (CMA) allows the identification of copy number variations. We performed a systematic review and meta-analysis of the literature, studying the incremental diagnostic yield of CMA in fetal isolated CVM, scoring yields for each category of heart disease, with the aim of guiding genetic counseling and prenatal management. At the same time, we report 59 fetuses with isolated CVM with normal karyotype who underwent CMA. The incremental CMA diagnostic yield in fetuses with isolated CVM was 5.79% (CI 5.54–6.04), with conotruncal malformations showing the higher detection rate (15.93%). The yields for ventricular septal defects and aberrant right subclavian artery were the lowest (2.64% and 0.66%). Other CVM ranged from 4.42% to 6.67%. In the retrospective cohort, the diagnostic yield was consistent with literature data, with an overall CMA diagnostic yield of 3.38%. CMA in the prenatal setting was confirmed as a valuable tool for investigating the causes of fetal cardiovascular malformations.

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“…34 Although CMA has shown great values in prenatal diagnosis, this assay may detect VOUS, pathogenic CNVs in adulthood, and disease carriers. 35 Results from the NICHD trial showed that CMA identified 1.8% of the study fetuses with possible benign CNVs and 1.6% with possible pathogenic CNVs. 36 This VOUS may be attributed to rare or new CNVs, or due to variable penetrance.…”

mentioning

confidence: 92%

Effectiveness of Chromosomal Microarray Analysis for Prenatal Diagnosis of Fetal Echogenic Intracardiac Focus: A Single-Center Experience

Huang¹,

Cai²,

Liu³

et al. 2021

IJGM

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Background: Echogenic intracardiac focus (EIF) is a common ultrasound finding during pregnancy. However, the correlation between fetal EIF and cardiac abnormality remains in dispute until now. The study aimed to examine the association of fetal EIF with chromosomal abnormality by means of chromosomal microarray analysis (CMA). Materials and Methods: A total of 192 pregnant women with fetal EIF undergoing amniocentesis or umbilical cord blood puncture were recruited and assigned into groups A (8 cases with isolated EIF alone), B (75 cases with EIF and other cardiac malformations) and C (109 cases with EIF and extracardiac malformations). All fetuses underwent karyotyping analysis and CMA simultaneously. The detection of chromosomal abnormality and copy number variations (CNVs) were compared. Results: Chromosomal karyotyping identified 5 fetuses with chromosomal abnormality, including 3 cases with trisomy 21, one fetus with Turner's syndrome, and one fetus with chromosome 8 mosaicism, while CMA detected 6 additional fetuses with CNVs, including 2 fetuses with pathogenic CNVs and 4 fetuses with variants of uncertain significance (VOUS). There was no significant difference among groups A (0), B (5.33%) and C (6.42%) in terms of the prevalence of chromosomal abnormality (P> 0.05). Among the 4 fetuses with VOUS, pregnancy continued in 2 fetuses, and pregnancy was terminated in other 2 fetuses. Conclusion: An isolated EIF may not correlate with chromosomal abnormality. However, CMA is recommended in fetuses with CMA complicated by other abnormal cardiac ultrasound findings, which facilitates the prediction of fetal outcomes during the genetic counseling and precision assessment of prognosis.

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Chromosomal Microarray in Prenatal Diagnosis: Case Studies and Clinical Challenges

Cited by 4 publications

References 38 publications

Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges—Systematic Review of the Literature and Meta-Analysis

Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges—Systematic Review of the Literature and Meta-Analysis

Chromosomal Microarray Analysis in Fetuses Detected with Isolated Cardiovascular Malformation: A Multicenter Study, Systematic Review of the Literature and Meta-Analysis

Effectiveness of Chromosomal Microarray Analysis for Prenatal Diagnosis of Fetal Echogenic Intracardiac Focus: A Single-Center Experience

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