Advancing clinical access to whole genome sequencing

One in 10 Americans — half of them children — have a rare disease. Timely diagnosis is critical, but children often endure years of medical appointments and genetic testing for rare diseases before receiving a diagnosis. The delay to diagnosis can hinder access to treatment, impacting both the health outcomes for the child and the experience of the family.

Thanks to a powerful collaboration between Illumina, a leader in next-generation sequencing and genomic solutions, and Optum, a company focused on providing industry-leading expertise in everything from assessing clinical needs to generating clinical evidence, more families may be able to bypass the difficulties of a long diagnostic odyssey.

Together, Illumina and Optum are using an evidence-based approach to expand patient access to whole genome sequencing (WGS). It’s a turning point for patients and their families that has the potential to reshape the diagnosis and path to treatment for many rare and previously undiagnosed disorders. 

In rare pediatric diseases, molecular diagnostics has evolved rapidly. Single-gene testing to detect specific genetic changes was once the only testing method available. Not anymore. Now, DNA sequencing panels targeting multiple genes at the same time are becoming more common and more affordable.

For patients suspected to have a rare disease, the standard of care is often to target testing to the condition that is highest suspicion. However, single-gene tests, condition-specific panels and even chromosomal microarray analysis (CMA) provide limited information.

Modern tests have made it possible to use tests like whole exome sequencing (WES) to look at the coding part of genes, or about 1–2% of a patient's genome. More recently, WGS has been used to look at both coding and noncoding regions.

WGS is a more comprehensive test, capable of detecting and diagnosing a broader range of conditions. Instead of examining only 1–2% of a genome, WGS analyzes ~90% — supplying all the information from WES and CMA combined, plus additional insights in structural and other potentially causative alterations.

WGS is particularly valuable for children because most rare genetic diseases are present during childhood, where appropriate early interventions may lead to a lifetime of benefits. WGS also has potential to provide diagnoses for children and adults with longstanding medical issues of uncertain origin.

It’s another step forward in the personalized, precision medicine that is poised to become standard medical practice as this technology advances and the guideline-recommended use of testing increases.

Children presenting to pediatricians with developmental delays or intellectual disabilities may face a long road of nongenetic diagnostic tests and procedures.

When a child is eventually suspected to have a genetic disease, some physicians recommend a CMA or a small, condition-specific panel first; others opt to refer patients for additional testing by relevant specialists.

Patients who receive no genetic testing or have a negative result from initial testing may, unfortunately, experience what is called a “diagnostic odyssey.” A diagnostic odyssey is the long and difficult journey that many children with rare diseases and their families undertake to receive an accurate diagnosis.

On average, these journeys can take 4 to 5 years. During their odyssey, patients typically will receive multiple blood tests, condition-specific panels, imaging studies and multiple specialty referrals. Unfortunately, many may receive multiple misdiagnoses as well.

Additionally, according to studies, children without a definitive diagnosis often don’t get the follow-up evaluations they need. For this reason, WGS may be preferable to CMA, WES and narrow condition-specific panels, as it can be used in place of all these tests where clinically indicated.

Thanks to a 2023 medical policy change, qualifying UnitedHealthcare beneficiaries now have coverage for WGS in the outpatient setting. But that is just a first step. Despite the increased need and demand for comprehensive genetic testing, patients still struggle to access testing for many reasons. More needs to be done to ensure that the people who can benefit from WGS are made aware of their eligibility for testing.