About one in 250 women are carriers of the Fragile X gene premutation which causes intellectual disability
All women planning a family should be screened to determine their Fragile X carrier status, according to researchers at the Murdoch Childrens Research Institute.
Fragile X was the most-common known inherited cause of intellectual disability, and also the largest known single gene cause of autism spectrum behaviour, Dr Jonathan Cohen, a leading Fragile X researcher, said.
Dr Cohen and colleagues are calling for guidelines to recommend all women to have Fragile X carrier screening, instead of only if they have a family history, or if they specifically request testing.
“Fragile X is a dominant gene, so the carrier could be either parent, but it only becomes a problem when mum is the carrier and they have a risk of the gene expanding in utero to have an affected fetus.”
Approximately one in 250 women are carriers of the premutation, and most carriers did not have a family history, Dr Cohen said.
Mothers who are carriers have a 50% chance of passing the premutation on. And 50% of these will expand into the full mutation in utero, depending on the length of the gene.
“The small expansions have a lower risk of expanding to a full mutation, the larger expansions have a higher risk,” Dr Cohen said. “So the risk can vary from 5% to 100% depending on the length of the gene.”
Around 50 people were estimated to be born with a full mutation in Australia every year. This affected not only include intellectual disability but also behavioural issues, such as major anxiety disorders, ADHD and autism spectrum behaviours, he said.
“And because most of the kids look normal, it just presents as behavioural problems and they’re often missed.”
The advantage of offering the screening more broadly is that women can be tested before pregnancy, providing them with a full range of reproductive options, including preimplantation genetic diagnosis (PGD).
In addition, female carriers of the premutation had a high risk, around 20% or more, of premature ovarian insufficiency, Dr Cohen said, which had a significant impact on fertility.
Women in Victoria are currently able to screen for Fragile X, in conjunction with other conditions such as cystic fibrosis, for a few hundred dollars.
But while current guidelines recommend screening in those with a family history, authorities have been reluctant to recommend screening for the general population.
Speaking on behalf of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Dr Will Milford said that the college welcomed the development of these new tests but cautioned they needed to be administered in the correct fashion.
“Women need counselling appropriately before and after testing, and that’s where this gets difficult, particularly because many pregnancies aren’t planned,” he said.
“So the question is, do you screen in early pregnancy, which could cause anxiety about the continued pregnancy?”
And with the expense of testing, there was also a concern about equity, he said.
More widespread screening would also require coordinated training for GPs, who would do the bulk of counselling, Dr Milford added.
However, Dr Cohen said a survey of more than 1000 women recently undertaken by the research institute showed “with absolute clarity that this test can be offered without causing psychological harms”.
Rates of regret and decisional conflict were low when women were asked about their decision a month after being offered screening and pre-test counselling.
Dr Cohen was also unconcerned about the added burden of testing and genetic counselling, explaining that if all 70,000 births in Victoria per year had been accompanied by Fragile X carrier screening, only 280 women would have been found to be carriers.
