Mater Pathology

Can Paediatric Cytogenetic Microarray testing be requested by general practitioners?

January 27, 2016

Whilst in some complex cases the involvement of a Paediatrician or Neurologist may be necessary, paediatric neurodevelopmental testing can also be requested by the family doctor, just like karyotype testing.

Microarray testing is available at Mater Pathology for the diagnosis of patients with intellectual disability, developmental delay, autism or congenital abnormalities, and is rebatable through Medicare.

Mater Pathology also provides consultation over the phone to assist with interpretation of results.

Microarray testing has been recommended by the American College of Medical Genetics (ACMG) as the first tier test [i] for the investigation of individuals with unexplained developmental delay/intellectual disability, autism spectrum disorders or two or more congenital anomalies

Why do a microarray instead of a karyotype?

Aneuploidy or large unbalanced chromosome rearrangements are often found in the above patients by karyotype, however many pathogenic rearrangements are below the resolution of this test. Microarrays offer a high resolution and genome wide method for detecting copy number changes (such as deletions and duplications).

What array type does Mater Pathology use?

Mater Pathology uses the Affymetrix 750K SNP array which has a total of 750,000 probes consisting of approximately 550,000 probes to allow for the detection of copy number changes at an effective resolution of approximately 100 kb. The Affymetrix SNP array has an added benefit over CGH-arrays used by some other providers in also having ~200,000 SNP probes which detects regions of long contiguous stretches of homozygosity (LCSH) which can be an indicator of uniparental disomy (UPD) or regions which are identical-by-descent (IBD).

What type of results can you expect?

1. No copy number changes (CNC) detected.

Many results will have no changes detected and the cause of the patient’s illness remains unexplained. Microarrays can NOT detect single gene mutations, disorders such as Fragile X syndrome, CNC’s below the array resolution or cases where there is low level mosaicism. Microarrays also do NOT detect balanced rearrangements however this is unlikely to be associated with an abnormal phenotype. 

2. A copy number change is detected.

Different types of CNC’s may be detected including:

a) A pathogenic CNC

  • ‚ÄčA deletion or duplication of known clinical significance with a recognised phenotype.

b) A variant of uncertain significance

  • A region which has been described in individuals with developmental delay/intellectual impairment, but is also been found in unaffected individuals and family members. Genes within these regions may show incomplete penetrance or variable expressivity and the clinical significance of these regions has not been fully elucidated.

c) A variant of unknown significance

  • A region which has not been well described in the literature or in relevant databases and the significance of which is unknown.

d) Incidental finding

  • A copy number change that is unrelated to the clinical presentation of the individual but has clinical significance.

3.  A region/s of LCSH has been detected.

Large regions of LCSH on a single chromosome may be an indicator of UPD. This is of potential clinical significance when the chromosome involved is imprinted, such as chromosome 15 in association with Prader Willi/Angelman syndrome.

Multiple regions of LCSH on several chromosomes may be an indicator of consanguinity. Such individuals are at risk of a recessively inherited single gene disorder which may require further assessment via a clinical genetics service.

Practical Information:

Specimen requirements: 5mls of peripheral blood in an EDTA tube and a Mater Pathology request form for microarray testing with any relevant clinical information noted. Such information is essential when trying to interpret copy number changes.

Billing: A Medicare item number is available for this test. No out of pocket fees apply.

Further Information: If you would like to find out more about microarray testing or would like to discuss your patient’s results, please contact the Cytogenetics Department at Mater Pathology on 07 3163 8498 / 3163 5988.

View this and additional information on Paediatric Neurodevelopmental genetic testing as PDF file, available for printing and download.