Maddie Thwaites remembers staring at the wall as a genetic counsellor shared the results of a cheek swab she and her husband, Ciaran McAuley, had done two months earlier and had thought little about since.
In a moment of powerful prescience, the couple were told they carried the same rare gene mutation that meant any child they conceived had a one-in-four chance of having a deadly neurodegenerative disorder.
Maddie Thwaites and Ciaran McAuley with their two-year-old daughter, Mairead.Credit: Joe Armao
“We would have been completely blindsided,” Thwaites said. “Neither of us has any family history of genetic disorders.”
The Thwaites were one of 9107 couples screened for 1300 genes linked to over 750 rare childhood-onset diseases by the Mackenzie’s Mission project – an unprecedented-in-scale study exploring the feasibility of a nationwide, voluntary genetic reproductive carrier screening program.
The study published on Thursday in the New England Journal of Medicine found 1.9 per cent (almost one in 50 couples) were at high risk of having children with one or more of these conditions – only slightly higher than they would expect to find in the general population.
Yet 80 per cent of the affected couples were carriers for genetic conditions that would not have been picked up by the Medicare-funded genetic carrier test introduced in November 2023 that screens for spinal muscular atrophy (SMA), cystic fibrosis and fragile X.
The finding bolsters calls for the federal government to establish a free expanded carrier screening program.
Rachael Casella, whose daughter Mackenzie – the inspiration for Mackenzie’s Mission – died of SMA at seven months old, said every couple should have access, regardless of their means, location, cultural background or their doctor’s views.
“I want to jump up and down and shout: ‘Do you understand how important this is, and the impact this could have on families?’” Casella said.
Project co-lead Professor Martin Delatycki at the Murdoch Children’s Research Institute said Australia could be a world leader, envisioning an expanded genetic reproductive carrier screening initiative akin to the National Bowel Cancer Screening Program.
“By not offering a bigger gene panel, we know that children will be born with these conditions and that many, but by no means all, couples would want to take steps to avoid that,” Delatycki said.
Rachael and Jonny Casella with their sons Izaac and Joshua, and a photograph of their daughter Mackenzie who is the namesake of Mackenzie’s Mission.
The federal government-funded study, co-ordinated by Australian Genomics, provided affected couples with counselling sessions with genetic counsellors, clinical geneticists, and other medical specialists who explained their results, enabling couples to process the information, ask questions and make informed decisions.
About 83 per cent of affected couples who were not yet pregnant chose to undergo a free IVF cycle, test their embryos (known as preimplantation genetic testing) and use only unaffected embryos to have children.
The Thwaites were among them after learning that they were carriers for a disorder that killed most affected children before they had finished primary school.
“This was more heartache and grief than we were willing to risk,” Maddie said.
“Now that we have our daughter, I am just so thankful that we get to be parents,” she said, having conceived Mairead, now aged two, from their first IVF embryo transfer. “It drives home just how lucky we are.”
Couples could otherwise choose to conceive without IVF and undergo prenatal testing or test their child after birth. They could also choose to use donor eggs, sperm or embryos, adopt or choose not to have children.
“A decent number of affected couples decided not to intervene, and we very much respect that,” said co-lead researcher Dr Edwin Kirk at NSW Health Pathology and UNSW.
“This is about empowering people to make informed decisions,” he said.
The gene panel included a small proportion of severe conditions that could be effectively treated with early diagnosis.
What kind of genetic risk did affected parents carry?
About 75 per cent were at increased risk of having a child with an autosomal recessive condition, which is when both parents carry the same mutation and have a one-in-four chance that their child will develop the corresponding genetic condition, and a one-in-two chance their child will be a carrier of that mutation.
The other 25 per cent were at risk of having children with conditions linked to the genes on the X chromosome, which tend to be more severe in male children and are usually passed down from the mother.
“There is a disease that affects the function of the adrenal gland where the first sign is a perfectly healthy baby collapses and dies, but if you know about it, it is very straightforward to treat,” Kirk said.
Expanded carrier screening is not routinely offered and is only available to those who can afford it through commercial laboratories, which charge $600 to $2000.
An application to the government’s Medical Services Advisory Committee for new Medicare item numbers for expanded screening was rebuffed in 2022, partly because more evidence was needed on the medical, ethical, and societal acceptance and costs of expanded testing and the need for culturally sensitive approaches, including Aboriginal and Torres Strait Islander peoples.
A spokesperson for the Department of Health and Ageing said representatives had met the Mackenzie’s Mission team several times since the decision to help address the outstanding concerns.
“This study shows we can offer reproductive carrier screening for literally thousands of genes covering many hundreds of serious conditions to all Australian couples who would want it wherever they live, in a timely way acceptable to the broad community,” Delatycki said.
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