RANZCOG has advised since 2019 that genetic carrier screening should be offered to all parents-to-be. And, since 1 November 2023, Medicare funding has been available for carrier screening for 3 of the most important conditions. So, what is genetic carrier screening, where does it fit in, who should have it and how much does it cost?
What is genetic carrier screening?
Genetic carrier screening is a blood or saliva test to find out if you are carrying a ‘recessive’ rogue gene which might result in serious disease in your baby. It is for people who have no family history of genetic disease. People with a positive family history should ask to be referred for genetic counselling rather than choose to have this testing done.
What sort of disease?
There are lots of ‘recessive’ single gene disorders. The most common are the blood conditions thalassaemia and sickle cell disease, other common ones include cystic fibrosis, spinal muscular atrophy and Fragile X mental retardation. Almost all are serious conditions which shorten life span and cause substantial health impairment during life.
'Recessive’?
‘Recessive’ means that the effect of the rogue gene is cancelled by the presence of a healthy copy of the same gene (noting that we have 2 copies of every gene we have except in the special case of X-chromosome genes in males. Males only have one copy of X-chromosome genes since their X-chromosome is paired with a Y-chromosome, whilst females have 2 X-chromosomes).
Wouldn’t there be a history in my family if I was a carrier for a terrible disease?
Nope. Most people only learn that they are carriers for a recessive condition when their first affected child is born. 90% of babies with recessive genetic conditions are born to parents with no family history of that disease. This can seem baffling until we understand the basics of genetic inheritance.
In general we have 2 copies of every gene, 1 from our Mum and 1 from our Dad. (As mentioned above, an important exception to this is genes located on the X-chromosome in males when typically there is only one copy). ‘Recessive’ conditions only show themselves if you have 2 ‘dodgy’ copies of the gene that codes for it (or, in the case of Fragile X, if the only copy you have is dodgy). If you have a single good copy of a gene, you don’t develop the disease concerned despite also having a dodgy copy, and you won’t know that you are a ‘carrier’ until an affected child is born.
If you and your partner are both carriers of the same disease, there is a 1 in 4 chance that any baby you produce will get the dodgy copy of the gene from each of you and develop the condition in question. A procreational game of Snap! most of us want to avoid winning.
What are the chances of being a carrier?
Around 1 person in 25 carries the gene for cystic fibrosis, 1 person in 40 the gene for spinal muscular atrophy and 1 woman in 250 carries the gene for ‘Fragile X’ intellectual disability. Carrier rates do however vary in different ethnicities for different diseases.
Presuming widespread implementation, the newly funded Medicare 3-gene testing program is expected to identify that 1 in 160 reproductive couples are at increased risk of cystic fibrosis, spinal muscular atrophy or Fragile X in their offspring because both partners carry matching rogue genes for the condition in question.
Haemoglobin disorders (thalassamias and sickle cell disease) are the most common single gene recessive disorders, with 7% of the world’s population carrying a rogue gene for one of these. These however are screened for routinely in every pregnancy by virtue of the ubiquitous baseline full blood examination.
When is the best time to get tested?
The suggested time to be tested is when you first start to plan a family, ideally before there is a baby on the way. It is possible however to be tested at any time.
If you are already pregnant, then it is best to tested as early as possible so as to allow testing of the current fetus if you are found to be high risk.
What conditions are tested for?
There are 2 options. You can choose to do the wholly funded limited genetic carrier screening for the 3 most common conditions (cystic fibrosis, spinal muscular atrophy, Fragile X) or (at cost) to do one of the more extended panels. Current options for the extended panel are to test 500 genes or more than 1000 genes. (For context, we have around 20 000 genes.)
How exactly does the information help me? What can I do with it?
The testing gives you information that helps you plan your reproductive life, or alerts you to potential problems if you are already pregnant.
It is important to understand that you can’t change your genetic make-up, nor the genetic make-up of any baby you are already carrying.
If as a couple you are identified as high risk for one or more of the screened conditions, the following options are open to you: -
*Choose to get pregnant and then have the fetus tested in utero at early gestation and proceed accordingly
*Choose to use IVF (using own eggs and sperm) and test the embryo before implantation to ensure not affected (‘pre-implantation genetic diagnosis’). It is also an option to choose to use donor eggs and/or sperm
* Choose to use intrauterine insemination using donor sperm which has been pre-screened so as to ensure the donor is not a carrier for the relevant condition
* Choose to not get pregnant
* Choose to adopt a child instead
Anything else I need to know?
With the funded limited genetic carrier screening (3 conditions), only the biological mother is tested at first. This is because Fragile X is an ‘X-linked disorder’, meaning that usually only females are carriers (because they have two X-chromosomes) whilst it is almost always ‘expressed’ in boys because they usually only have one X-chromosome.
If a woman is not a carrier for any of these 3 conditions then there is no need for the intended/expectant father to undergo testing. This is because Mum can only give a ‘good’ copy of the relevant genes to any baby produced (because that’s all she has), and so it doesn’t matter if Dad contributes a dodgy copy.
If Mum is found to be a carrier for any of the conditions, then testing of Dad must go ahead to be able to make any sense of the risk.
Under the extended panel, almost everyone proves to be a carrier for something, and so it is routine for both partners to be tested from the outset.
Turnaround time for test results is 2-3 weeks for the 3-gene test and 6 to 8 weeks for either of the extended panel options.
A finding of carrier status for Fragile X can have health implications for the carrier themselves (who is usually but not always biologically female). Female carriers of fragile X have a 1 in 5 a risk of early ovarian failure before the age of 40 (called Fragile X-associated Primary Ovarian Insufficiency - FXPOI). There is also a risk of a progressive neurological disorder in later life with shaking, balance problems and cognitive issues (Fragile X-associated Tremor Ataxia Syndrome - FXTAS). For female carriers, the risk of developing FXTAS is 1 in 5 or 6, whilst for male carriers that risk is doubled to 2 in 5. Being found to be a carrier for Fragile X can thus provide you with unwelcome and worrying news about your own future health risks, and affect your future insurability.
How much does it cost?
For Medicare-eligible patients, limited testing (3 conditions) is fully funded ('bulkbilled' by the laboratory), whilst the extended panel options costs from around $1000 (both partners/500 genes tested) to $1500 (both partners/ >1000 genes tested).
Want to know more?
Click here to read an article from The Age about genetic carrier screening including one couple's story .
Click here to access a podcast where I discuss genetic carrier screening including how it differs from non-invasive prenatal testing with my colleague Dr Moz.
Click here to read about the specific tests available from VCGS (Victorian Clinical Genetics Service).
Or, book an appointment with me if you are ready to go ahead or still have questions.
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