Cytogenomic SNP Microarray, Fetal

  • Identifies genomic abnormalities (eg, aneuploidy, deletions, duplications)
  • Performed on direct and cultured amniotic fluid and chorionic villus sampling (CVS) specimens
  • Rapid detection of aneuploidy involving chromosomes 13, 18, 21, X, and Y
  • If results of aneuploidy FISH panel are normal, genomic microarray analysis will be performed
  • If results of aneuploidy FISH panel are abnormal, chromosome analysis will be performed
  • Performed on uncultured amniotic fluid
  • Rapid detection of aneuploidy involving chromosomes 13, 18, 21, X, and Y
  • If results of aneuploidy FISH panel are normal, genomic microarray analysis will be performed
  • If results of aneuploidy FISH panel are abnormal, chromosome analysis will be performed
  • Performed on uncultured CVS
  • Chromosome analysis is used for detection of aneuploidy and other chromosomal abnormalities (eg, large deletions/duplications, translocations, inversions, marker chromosomes)
  • If results of chromosome analysis are normal, genomic microarray analysis will be performed
Related Tests

Other fetal testing for cytogenetic abnormalities

  • Rapid detection of aneuploidy involving chromosomes 13, 18, 21, X, and Y
  • Performed on uncultured amniotic fluid
  • Detection of aneuploidy and other chromosomal abnormalities (eg, large deletions/duplications, translocations, inversions, marker chromosomes)
  • Performed on cultured amniotic fluid
  • Rapid detection of aneuploidy involving chromosomes 13, 18, 21, X, and Y
  • Performed on uncultured CVS
  • Detection of aneuploidy and other chromosomal abnormalities (large deletions/duplications, translocations, inversions, marker chromosomes)
  • Performed on cultured CVS

Cytogenomic SNP microarray testing is used to identify genomic imbalances (deletions and duplications) and may be used to further characterize abnormalities identified by chromosome analysis, including unbalanced translocations, recombinant chromosomes, markers, and ring chromosomes. Regions of homozygosity (ROH) can also be identified. It is the recommended first-tier test for patients undergoing prenatal diagnosis for the indication of a fetal structural abnormality detected by ultrasound (unless the structural abnormality is strongly suggestive of a specific aneuploidy, in which case, karyotype with or without FISH may be offered before genomic microarray).

Disease Overview

Diagnostic Issues

  • Many abnormal phenotypes are associated with chromosomal imbalances
  • Chromosome analysis has limited ability to detect copy number abnormalities less than 10-20 Mb in size
  • Genomic microarray can detect chromosomal imbalances at a much higher level of resolution than standard chromosome analysis
  • Genomic microarray can detect ROH, which may indicate an increased risk for autosomal recessive (AR) disease for genes contained within the ROH, and/or the risk of an imprinting disorder due to uniparental disomy (UPD), or molar pregnancy
  • Identification of specific abnormalities may be helpful in medical management and planning for special needs

Test Interpretation

Diagnostic Yield

  • 100% for nonmosaic aneuploidy detectable by karyotype
  • Among cases with a normal karyotype, microarray studies reveal clinically relevant copy number variants (CNVs) in:
    • ~6% of fetuses with a structural anomaly, may be higher depending on anomaly
    • ~2% whose indication is advanced maternal age or positive aneuploidy screen
  • The diagnostic yield varies by patient population and the presence of comorbidities

Results

  • A written summary and an interpretation of the microarray findings are provided
  • CNV evaluation is performed in accordance with recommendations by the American College of Medical Genetics and Genomics (ACMG):
    • Standard 5-tier classification terminology is used:
      • Pathogenic
      • Likely pathogenic
      • Variant of uncertain significance (VUS)
      • Likely benign
      • Benign
    • Variants that do not fall within these categories may be reported with descriptive language specific to that variant
  • For a list of databases used in CNV classification, please refer to the ARUP Constitutional Copy Number Variant Assertion Criteria.
  • Submission of a maternal blood sample for maternal cell contamination studies is encouraged
Result Description

Normal

No clinically significant CNV or ROH detected

Abnormal

One or more clinically significant CNV, ROH, aneuploidy, or triploidy detected

Uncertain

One or more CNVs of uncertain clinical significance detected

  • Insufficient evidence for unequivocal determination of clinical significance available at the time of review
  • AR risk

Uncertain ROH: Risk for AR disease and/or imprinting disorder due to UPD

  • Testing may suggest relatedness between the parents of the tested individual

Reporting Criteria

  • Deletions >1 Mb and duplications >2 Mb are generally reported, dependent on genomic content
  • CNVs classified as VUS are generally reported when found to have suspected clinical relevance based on information available at the time of review, or when meeting size criteria
  • Total autosomal homozygosity >5% is generally reported
    • Only autosomal ROH >3 Mb are considered for this estimate
  • Single terminal ROH >3 Mb or single interstitial ROH >10-20 Mb are generally reported, dependent upon chromosomal location and likelihood of imprinting disorder
  • Recessive disease risk and recurrent CNVs with established reduced penetrance are generally reported
  • CNVs classified as likely benign or benign that are devoid of relevant gene content or reported as common findings in the general population are generally not reported

Limitations

  • Does not detect:
    • CNVs below the limit of resolution of the testing platform
    • Sequence-level variants (mutations), including point mutations and small insertions/deletions
    • Balanced chromosomal rearrangements (translocations, inversions, and insertions)
    • Imbalances of the mitochondrial genome
    • Low-level mosaicism (generally <20-30%)
    • Most cases of tetraploidy