🧬 Chromosomal Microarray Analysis in Prenatal Diagnostics
Now offered by Ampath Genetics
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
Abnormality TypeCMA ✅Karyotype ✅Aneuploidy✅✅Sub-microscopic CNVs✅❌Unbalanced translocations✅✅/❌Balanced rearrangements❌✅Triploidy❌✅
⚠️ 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 | ✉️ geneticsclinic@ampath.co.za