Takeaways:
- Evidence suggests whole genome sequencing to diagnose genetic diseases has a significant beneficial impact on patients and their families.
- Mayo Clinic and UnitedHealthcare are collaborating to help individuals with suspected rare disease, get the genetic testing they need through the Special Needs Initiative.
Whole genome testing speeds time to diagnosis
Coverage of a comprehensive diagnostic test known as whole genome sequencing offers hope to patients affected by rare genetic diseases. Now covered in the outpatient setting by UnitedHealthcare, Cigna and other regional plans for specific medical conditions, WGS can speed the time to diagnosis.
There are nearly 30 million individuals and families affected by rare diseases in the U.S. More than 70% of rare diseases are genetic and appear in childhood and often go undetected by health care professionals. Families spend, on average, four to five years visiting numerous specialists in search of a diagnosis. During this time, patients may even go undiagnosed several times, even as their symptoms become increasingly severe and disabling.
As a geneticist, I think as soon as a patient shows up and demonstrates that they have any type of medical complexity that suggests the possibility of a genetic disease, we should be considering WGS and offering testing so we can have clarity and get them on the right treatment path.
Brendan C. Lanpher, MD, Medical Geneticist, Mayo Clinic
With more than 10,000 rare diseases already identified and numerous novel gene associations discovered each year, patients with a suspected rare disease may benefit most from a single test that provides nearly comprehensive information about their genetics. WGS would be considered the most comprehensive test available. Unlike other genetic testing modalities, including sequential single-gene testing and whole exome sequencing, WGS sequences an individual’s entire genome and can detect the largest number of potentially disease-causing alterations.
The many uses of genome testing
WGS can be used to help identify a wide range of potential disease-causing genetic changes in pediatric patients with multiple congenital anomalies, intellectual disabilities or unexplained developmental delays. Rather than ordering a series of targeted gene tests, physicians may find using a comprehensive test preferable for patients with nonspecific clinical presentations. WGS has been shown to increase detection rate while decreasing the time to diagnosis. It produces extensive data for each patient that can be re-analyzed as new gene-disease associations are discovered.
Beyond diagnosis, WGS can provide important additional information about rare diseases to better guide treatment. In an example involving fraternal twins first diagnosed at age five with Dopa-responsive dystonia, WGS testing at age 14 identified a pathogenic variant in both children that inhibits the body’s ability to make dopamine and serotonin. This finding meant that they needed another medication, 5-HTP, added to the levodopa (L-Dopa) therapy they were receiving. After receiving the new treatment, the twins had better coordination, enhanced sleep and focus, and fewer laryngeal spasms. An earlier diagnosis of this pathogenic variant would certainly have reduced morbidity and could possibly have changed the course of the twins’ physical and intellectual development.
The value of whole genome sequencing to patients and families
Recognizing the value of WGS to patients and their families, in 2023 UnitedHealthcare became one of the first health insurance companies to offer coverage for the test in outpatient settings. In the year since, several families impacted by rare diseases have received an accurate diagnosis through WGS, leveraging United Healthcare’s coverage policy to reduce the associated cost, in many cases allowing for effective treatments to be offered earlier. In addition, WGS has helped clinicians rule out other suspected genetic conditions and focus elsewhere for the cause of a patient’s symptoms.
Recently published data supports using whole genome sequencing as a replacement for the combination of exome sequencing and chromosomal microarray as a first-line diagnostic test. The Broad Center for Mendelian Genomics and Boston Children’s Hospital performed whole genome sequencing on 822 families suspected to have a rare disease for whom prior genetic testing had not identified a genetic cause. Within this cohort, a molecular diagnosis was found in 218 families, with 61 families having causative variants that required WGS for identification. This compares favorably to the combination of exome and microarray for both its high detection rate and simplification of the testing procedure.
Whole genome sequencing is really an exciting culmination of a history of genetic testing that has evolved and continues to evolve very rapidly. At this point in time United Healthcare has reviewed the data and the evidence points to whole genome sequencing having a significant and beneficial impact in the genetic diagnosis for specific clinical conditions that are outlined in our policy.
Lucy Langer, MD, National Medical Director, Oncology and Genomics, UnitedHealthcare
All people deserve high-quality, affordable, accessible care. Those with rare diseases are no exception. Current evidence suggests that using WGS to diagnose genetic diseases has a significant beneficial impact on patients and their families. Physicians can research the benefits of WGS and use it to help diagnose complex conditions more rapidly and precisely. WGS is a crucial aid to helping find answers and alleviate suffering for those with rare diseases.
Learn more about how Mayo Clinic and UnitedHealthcare are collaborating to help pediatric and adolescent individuals facing serious or complex medical challenges, including those with suspected rare disease, get the care and genetic testing they need through the Special Needs Initiative.
Optum Evidence Engine provides industry-leading expertise in everything from assessing clinical needs to conducting retrospective studies. Learn more about Optum Evidence Engine.
About Lucy Langer and Brendan C. Lanpher
Lucy Langer, MD, is national medical director, oncology and genomics, UnitedHealthcare.
Brendan C. Lanpher, MD, is a medical geneticist, Mayo Clinic.
Optum Evidence Engine provides industry-leading expertise in everything from assessing clinical needs to conducting retrospective studies.