Screening for Fragile X Carriers May Be Cost-free Option for Couples in Australia

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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The Australian Medical Services Advisory Committee (MSAC) has recommended that the costs of screening for mutations known to cause cystic fibrosis (CF), spinal muscular atrophy (SMA), and fragile X syndrome be open to reimbursement for couples planning or in the early stages of pregnancy.

Its favorable opinion followed an application from the Royal College of Pathologists of Australasia (RCPA) seeking to add what is known as reproductive carrier screening for these genetic diseases to the Medicare Benefits Schedule (MBS), a listing of the Medicare services subsidized by the Australian government.

MSAC recommendations on whether medical services should be publicly funded — based on their safety, clinical effectiveness, and cost-effectiveness data — are reviewed by the country’s health minister. The government will now decide on the RCPA’s application, and if it agrees, will also set the level of funding and eligibility requirements.

“This is an extremely promising step forward and we are closer than ever to having these tests listed on the MBS,” Melody Caramins, PhD, the clinical leader of the application and former chair of the RCPA Genetics Advisory Committee, said in a press release.

“The addition of these items to the MBS would mean that asymptomatic couples with no family history of CF, SMA or FXS [fragile X syndrome], who are planning or in the early stages of pregnancy, would be able to access carrier screening at no personal cost,” Caramins added.

CF, SMA, and fragile X are three of the most commonly inherited diseases, and all significantly affect patients’ quality of life and that of their families.

Leading to progressive muscle weakness, SMA is one of the most common genetic causes of infant mortality, while CF, mainly impairing lung function, lessens life expectancies despite significant treatment advances in recent decades. Fragile X is the most common inherited cause of intellectual disability and autism spectrum disorder.

Both CF and SMA are inherited in an autosomal recessive manner, meaning a child must acquire two defective copies of a disease-associated gene — one from the mother and one from the father — to develop the disorder.

People with only one mutated gene copy are typically healthy, but are considered to be carriers because they can still transmit the mutated gene to their children. If both parents are SMA or CF carriers, their child has a 25% chance of developing the disease.

Fragile X syndrome is an X-linked dominant disorder caused by a mutation in a gene located on the X chromosome (one of the sex chromosomes). Since men only have one X chromosome, those who inherit the mutated gene will have more severe disease, while in women — who have two X chromosomes — a healthy gene copy can compensate for the mutated copy to a certain extent.

As such, women who are fragile X carriers have up to a 50% chance of having a child with this disease.

A previous study showed that 1 in 20 people in Australia are carriers of one or more of these disorders, but most “are usually unaware,” Alison Archibald, PhD, the study’s first author and a genetic counselor at Victorian Clinical Genetic Services (VCGS), said in a VCGS press release.

“Many children affected by these conditions are born to families with no history of disease, due to the rare nature of the conditions and patterns of inheritance,” Archibald added.

The combined chance of a child being affected with one of these diseases was also found to be comparable to that of Down syndrome — for which screening is offered as part of standard pregnancy care in most Western countries.

Identifying carriers of CF, SMA and fragile X is essential for genetic counseling of adults who are planning families, helping them to make informed reproductive decisions “in order to avoid or better manage having a child affected with the disorder,” Caramins said.

Reproductive carrier screening analyzes a couple’s saliva or blood samples to determine their risk of having a child affected by one or more inherited genetic conditions. Couples undergoing this type of testing are advised to discuss screening results with a genetic counselor, and to assess the need for further testing.

Caramins and colleagues in a previous study found that women living in areas of Australia considered by postal code to be most “advantaged” were significantly more likely to have reproductive carrier screening than those living in the most disadvantaged areas.

“Reproductive carrier screening is already being performed to a significant extent in Australia, but most patients are having to pay out-of-pocket, and this is a significant health equity issue,” Caramins said.

In the VCGS’s release, Archibald said that research conducted at that service and the Murdoch Children’s Research Institute showed that “health professionals, people having screening, and people and families impacted by these genetic conditions support that this screening being made widely accessible, provided it is optional.”

Notably, SMA Australia, Cystic Fibrosis Community Care, and the Fragile X Association of Australia all support offering reproductive carrier screening for these three diseases, and have endorsed the RCPA application and MSAC recommendation.

The Royal Australian and New Zealand College of Obstetricians and Gynaecologists and Human Genetics Society of Australasia also recommend that every woman considering pregnancy be offered information about carrier screening for CF, SMA, and fragile X.

A nationwide reproductive genetic carrier screening study, called Mackenzie’s Mission, is currently underway in Australia. Its aims to determine the best way to deliver reproductive carrier screening freely to all Australians who want it. Couples who volunteer to join the study will be screened for genetic mutations that raise their risk of having a child with any of roughly 750 disorders.