Chromosomal Microarray Analysis in Prenatal Diagnostics
Dr Lindsay Lambie | Ampath Chat No. 99
Background
Traditional karyotyping has long been the standard for prenatal cytogenetic analysis but is limited to detecting large chromosomal abnormalities (>5–10 Mb).
Chromosomal Microarray (CMA), introduced in the early 2000s, allows high-resolution, genome-wide analysis of copy number variations (CNVs), including sub-microscopic deletions and duplications.
CMA is now endorsed as a first-tier test by ACOG, SMFM, and the Royal College of Pathologists for specific prenatal indications.
When is Prenatal CMA Recommended?
CMA can replace standard karyotyping in cases such as:
- Foetal structural anomalies on ultrasound (e.g. cardiac, CNS, skeletal)
- Increased nuchal translucency or soft markers
- Unexplained intrauterine growth restriction (IUGR)
- Normal karyotype but ongoing suspicion of a genetic condition
- Family history of chromosomal rearrangements
- Intrauterine foetal death or stillbirth (when common causes are excluded)
How Does Array CGH Work?
Ampath uses Array Comparative Genomic Hybridization (Array CGH), not SNP arrays.
- DNA from the foetus (via amniotic fluid or CVS) is compared to reference DNA
- Fluorescent dyes highlight deletions/duplications
- Ampath uses the Agilent GenetiSure 60K CGH platform with ~60,000 probes
CNV Analysis & Reporting
- CNVs are analyzed using Agilent Cytogenomics software
- Classified per ACMG and ClinGen standards
- Only pathogenic/likely pathogenic variants relevant to the clinical picture are reported
- Incidental findings are reported only if clinically actionable
- Interpretation is done by a multidisciplinary team including geneticists and counsellors
Diagnostic Yield
- CMA increases diagnostic yield by 6–10% over karyotyping in pregnancies with ultrasound anomalies
- Especially effective when anomalies span multiple organ systems
- ACOG recommends CMA as the first-tier test in such cases
CMA vs. Karyotyping
Limitations of CMA
- Cannot detect balanced rearrangements or triploidy
- May miss low-level mosaicism or point mutations
- Cannot distinguish between different genetic mechanisms (e.g. trisomy vs. translocation)
Counselling & Consent
Before testing, patients should be informed about:
- Test scope and limitations
- Possibility of incidental findings
- Need for parental testing in some cases
Informed written consent is required. A dedicated request form is provided.
Key Information
- Test mnemonic: ACGHPREN
- Sample requirements:
- CVS or 15–20 ml amniotic fluid or 3 ml cord blood
- Maternal EDTA blood to exclude maternal cell contamination
- Documentation:
- Completed prenatal genetic request form
- Signed patient consent
- Turnaround time: 2 weeks (if no culture required)
Conclusion
CMA is a high-resolution, first-tier genetic test for specific prenatal indications.
Karyotyping or rapid PCR remains useful when common aneuploidy is suspected.
Collaboration between clinicians and the lab is key.
Genetic counselling is available on referral.
Contact: 012 678 0645