Genomics in general practice

Genetic tests and technologies

Chromosome microarray

Chromosome microarray

What is it?

A chromosome microarray (CMA; also known as a chromosomal microarray or molecular karyotype) is a powerful diagnostic tool that is used to identify genetic causes of illness and developmental problems. It is used to quantify the number of copies of thousands of segments of DNA simultaneously. A CMA can identify small segments of missing or extra deoxyribonucleic acid (DNA), known as copy number variants (CNVs).

Some CNVs have been linked with certain conditions, while others represent normal human variations. Some CNVs are associated with an increased risk of morbidity but can be seen in healthy individuals. There are also some CNVs for which the clinical impact is unknown or uncertain.

Why use it?

CMAs are commonly used in two clinical situations, as a:

  • prenatal diagnostic test
  • first-line test for individuals presenting with developmental delay (DD), intellectual disability (ID) with or without facial dysmorphism, autism spectrum disorder (ASD) or multiple congenital anomalies 

The use of CMAs has grown given they have much greater resolution than traditional karyotypes (ie can detect much smaller variations and provide a greater diagnostic yield, compared with a traditional karyotype which involves examination of chromosomes under the microscope).

What does CMA test for?

CMA only tests for variations in DNA copy number. It can identify:

  • large deletions and microdeletions and large duplications and microduplications
  • most abnormalities of chromosome number (eg Down syndrome)
  • unbalanced rearrangements of chromosome (eg complex insertions or deletions).

However, it does not identify:

How does it work?

CMAs are performed using a blood sample, or in some cases, saliva. Testing uses a microchip platform, which allows the analysis of many pieces of DNA at once. The microchip uses labels or probes that bind to certain chromosome regions. Analysis compares the patient’s DNA sequence with a reference DNA sequence. Any differences are called ‘variations’.

Should I order a CMA (or simply refer)?

In the prenatal setting, many women who undergo an invasive procedure (eg chorionic villus sampling [CVS], amniocentesis) will have their sample analysed using a CMA (in addition to fluorescence in situ hybridisation [FISH] or quantitative fluorescence polymerase chain reaction [QF-PCR]). General practitioners (GPs) working in this area may see the results from CMAs; the section on interpretation of results below may be useful.

There are no clear guidelines about whether GPs should be ordering CMAs for investigating DD or ID in children. A CMA has been identified as a first-line test for investigating non-syndromic DD and ID. A Medicare Benefits Schedule (MBS) rebate is available for CMAs in the paediatric setting where a patient has DD, ID, ASD or at least two congenital abnormalities.

While GPs are able to order CMAs themselves, many choose not to given the complex interpretation of the results. However, ordering a CMA (together with an FXS test) alongside a referral to a specialist can reduce waiting times for patients. It is important to note that microarrays will not identify FXS; a separate DNA test is required.

What do the results mean?

In general, the results of a CMA are shown in Table 1.

Table 1. CMA results

No clinically significant copy number variants (CNVs)

Pathogenic or likely pathogenic CNV

CNVs of uncertain Significance

Secondary or unexpected findings

Normal result

Known copy number variant identified

Copy number variant(s) of uncertain significance (VOUS) identified. Clinical impact is unknown or uncertain

Copy number variant identified that is unrelated to the reason for testing


Laboratory report will suggest next steps (eg referral to genetics, family testing)

Laboratory report will suggest next steps (eg referral to genetics)

Laboratory report will suggest next steps (eg referral to genetics, family testing)

Further reading

  • Martin CL, Ledbetter DH. Chromosomal Microarray Testing for Children With Unexplained Neurodevelopmental Disorders. JAMA. 2017;317(24):2545-2546. doi:10.1001/jama.2017.7272
  • Palmer EE, Peters GB, Mowat Chromosome microarray in Australia: A guide for paediatricians. J Paediatr Child Health 2012;48(2):E59–67.
  • Miller DT, Adam MP, Aradhya S, et Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86(5):749–64.
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