World’s Largest Newborn Screening Study to Include Fragile X Syndrome

Fragile X syndrome is among the four rare genetic disorders to be included in the world’s largest newborn screening study for rare diseases.

The screening, financially supported by the Angelman Syndrome Foundation, the Foundation for Prader-Willi Research and the Victorian Medical Research Acceleration Fund, will also include Angelman, Prader-Willi, and Dup15q syndromes.

A pilot study that will include screening of 75,000 newborns will establish the feasibility of the test for  large-scale screening. The study will be led by Associate Professor David Godler from the Murdoch Children’s Research Institute in Melbourne, Australia.

“Having a cost-effective test to accurately diagnose these syndromes in the newborn period is key to ensuring that families receive optimal medical care and support,” Theresa Strong, director of research programs for Foundation for Prader-Willi Research, said in a news release. “The study will validate the newborn screening tool so that, once approved for use, it can be used to screen all babies in the newborn period.”

The screening is based on earlier work from Godler’s team to develop a test that can accurately diagnose fragile X syndrome. The test, called methylation specific-quantitative melt analysis (MS-QMA), can quantitatively assess DNA methylation, which silences the FMR1 gene.

Using blood spots from newborns, researchers were able to diagnose fragile X syndrome with a specificity and sensitivity varying between 92  and 100 percent.  These initial results were published in Clinical Chemistry in a study titled “Early detection of fragile X syndrome: applications of a novel approach for improved quantitative methylation analysis in venous blood and newborn blood spots.”

The additional funding will allow researchers to assess the test’s efficacy for other rare diseases, like Angelman syndrome — a complex neurological genetic disorder caused by defects in the UBE3A gene — Prader-Willi and Dup15q syndromes — neurological disorders caused by a fault in a group of genes on chromosome number 15.

“I believe the prevalence of these disorders is underestimated, because all tests used to diagnose these conditions were developed more than 10 years ago and are not as sensitive,” Godler said.

The MS-QMA test is being tested in samples of 100,000 babies, thanks to an Australian National Medical Research Council grant and an Australian Federal Government’s Medical Research Future Fund fellowship of $800,000 and $500,000, respectively.

“Newborn screening means families with loved ones with Angelman, Prader-Willi, Fragile X and Dup15q syndromes will find a diagnosis in weeks instead of years, avoiding a painful diagnostic journey. And, if we can diagnose individuals earlier, we have the best chance of reversing the effects and improving their quality of life much sooner,” said Eileen Braun, executive director of the Angelman Syndrome Foundation.

If the test proves successful, “it would allow individuals to have standard-of-care therapies right from the beginning,” said Jessica Duis, MD, MS, Director of the Comprehensive Angelman Syndrome and Prader-Willi Clinics at Vanderbilt University Medical Center.