Reproductive genetic carrier screening - clinical fact sheet and MCQ

Reproductive genetic carrier screening (RGCS) is a type of genetic testing offered to individuals and their reproductive partners (including sperm or egg donors) to determine the chance of having a child with one of the screened inherited conditions. These are typically autosomal recessive (AR) and X-linked (XL) conditions that present in infancy or childhood and result in serious health complications.

In people of European ancestry in Australia, 1 in 20 carry one of the three most common genetic conditions: cystic fibrosis (CF), spinal muscular atrophy (SMA) and fragile X syndrome (FXS) [1]. This equates to a 1 in 240 chance of both reproductive partners being a carrier for one of these three conditions [1]. If both reproductive partners are a carrier for the same AR condition, or the female reproductive partner is a carrier for an XL condition, there is a 1 in 4 chance of having an affected child.

Image 1: autosomal recessive and X-linked inheritance patterns (source: https://www.racgp.org.au/getmedia/db5d54a8-1e8c-4c3f-9b8b-51fa457c767c/Genetic-carrier-screening_1.pdf.aspx)

Who should be offered RGCS

RANZCOG recommends that information on RGCS should be offered to all people planning a pregnancy, or in the first trimester of pregnancy, whether or not there is a known family history of a genetic condition [2].

When should RGCS be offered

It should be offered pre-pregnancy or in the first trimester of pregnancy.

Testing options

1. Three-gene panel

• This panel screens for the three most commonly inherited genetic conditions in Australians with European ancestry - CF, SMA and FXS

• All females are able to access a Medicare Benefits Schedule (MBS) rebate for this test (MBS item 73451) so there is no out-of-pocket cost

• Male reproductive partners can also access a MBS rebate (MBS item 73452) for CF and SMA screening if the female reproductive partner is confirmed as a carrier of one of those AR conditions

2. Expanded panel

• This panel screens for hundreds of AR and XL conditions (including CF, SMA and FXS) involving over 1,000 genes selected due to the severity of conditions and childhood onset

• This panel may be more appropriate for people of non-European or mixed ancestry as they improve detection of conditions more prevalent in diverse populations

• There is no MBS rebate and people will pay an out-of-pocket fee

• Screening can be performed sequentially (screen the female first and then screen the male reproductive partner if the female partner is a carrier of an AR condition) or concurrently (screen both reproductive partners at the same time)

• Concurrent testing is more time-efficient, but also more expensive

• Laboratories differ regarding the number of conditions and genes screened as well as the cost and the turnaround time of the test
  
  

Pre-test counselling

This should cover:

• RGCS is optional

• limitations of RGCS

• not all conditions, genes, or gene changes are included – a ‘low chance’ result does not exclude all risk

• it does not screen for chromosomal conditions, such as Down syndrome, in a pregnancy. Non-invasive prenatal testing/screening (NIPT/S) is available for this purpose
  
  

Considerations for choosing between the three-gene or expanded panel

It can be challenging for GPs and patients to choose between the three-gene or expanded panel, and to identify which pathology provider to use. The below factors can be considered when making these decisions.

No single pathology provider or testing laboratory is recommended over any other and offerings change frequently. A list of available pathology providers can be found here and is current at the time of publication.

Interpreting the results

The below table outlines the possible results.

Post-test counselling

Post-test counselling topics differ based upon the combination of results received for the reproductive partners.

1. Low chance results

• Provide reassurance, while clearly communicating residual risk

• Emphasise the importance of first and second trimester anatomy ultrasounds and standard antenatal care

• Public genetics services typically do not accept referrals for low chance results. If required, consider private genetic counselling or the referral pathway for genetic counselling offered by the testing provider. A list of private genetic services can be found here
  
  

2. Increased chance results

• People should be referred to a clinical genetics service for comprehensive genetic counselling. If a patient is already pregnant, this referral should be marked urgent and expedited
• Your patient’s local clinical genetics service can be identified here [3]
• Reproductive options for non-pregnant patients include in vitro fertilisation (IVF) with preimplantation genetic diagnosis/testing (PGD/T) [4], prenatal diagnostic testing via chorionic villus sampling or amniocentesis [5], use of donor gametes, adoption, or electing not to have children
• Cascade screening should also be recommended for at-risk relatives
  
  

3. If a fragile X premutation is identified:

• there are associated personal health implications for individuals with a fragile X premutation, where the FMR1 gene contains 55 to 200 CGG repeats—fewer than the >200 repeats that result in full fragile X syndrome
• female premutation carriers of FXS may develop fragile X-associated primary ovarian insufficiency (FXPOI) whilst female and male premutation carriers may develop fragile X-associated tremor/ataxia syndrome (FXTAS) [6]
• these patients should be referred to clinical genetics for further evaluation and discussion regardless of their chance of having an affected child

References

1. Dalton Archibald A, Smith MJ, Burgess T, et al. Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests.Genet Med;2018;20(5):513-523.

2. Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). Genetic carrier screening. Melbourne: RANZCOG; 2024. Available at: https://ranzcog.edu.au/wp-content/uploads/Genetic-Carrier-Screening.pdf. (last accessed August 2025).

3. Centre for Genetics Education. Genetic services. Sydney: NSW Health; 2022. Available from: https://www.genetics.edu.au/SitePages/Genetic-Services.aspx. (last accessed August 2025).

4. Centre for Genetics Education. Pre-implantation genetic diagnosis. Sydney: NSW Health; 2022. Available from: https://www.genetics.edu.au/publications-and-resources/facts-sheets/fact-sheet-17-preimplantation-genetic-diagnosis. (last accessed August 2025).

5. Centre for Genetics Education. Diagnostic tests during pregnancy. Sydney: NSW Health; 2022. Available from: https://www.genetics.edu.au/publications-and-resources/facts-sheets/fact-sheet-18-diagnostic-tests-during-pregnancy. (last accessed August 2025).

6. Fragile X Association of Australia. Fragile X permutation carriers. 2025. Available at: https://www.fragilex.org.au/understanding-fragile-x/fragile-x-premutation-carriers/. (last accessed August 2025).

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