For medical practitioners expertly trained in the scientific methods of discovery, having a young patient with serious health complications from an undiagnosed condition is about as somber and frustrating as it gets. These feelings are only magnified for parents of the patient, especially when searching for a diagnosis can go on for years. This is the essence of what is known as the “diagnostic odyssey.”
Honing in on a rare disease diagnosis involves thorough medical history evaluations, genetic and other testing, medical records review, in-person interviews, physical examinations, and evaluations of family members with similar symptoms. This process can be repetitive because primary doctors will refer to specialists who may, in turn, refer to other specialists if no answers can be found. But with accessibility to whole genome sequencing (WGS), a technology that can help end the diagnostic odyssey with a single test, it doesn’t have to be this way.
Dr. Nelson Sanchez of First Choice Neurology is a pediatric neurologist who has been using whole genome sequencing (WGS) as the method of choice to solve many diagnostic puzzles. This has come about from his personal experience with a challenging case, a young patient caught in a decade-long diagnostic odyssey. Despite all attempts to manage his symptoms, the patient failed to respond sufficiently and eventually had to be placed in a medically induced coma.
Fortunately, WGS was able to identify the rare inherited disorder that was behind the symptoms, opening up new treatment options which ultimately led to the patient being brought out of the coma. Dr. Sanchez has adopted the notion that a single WGS test ordered at the start can provide more useful diagnostic data regarding the relevant genes and variants without having to run multiple tests.
“Patients that use whole genome sequencing for testing at my office are typically looking for a diagnosis for progressive neurological disorders, seizure disorders, autism, epilepsy, and others,” said Dr. Sanchez. “When patients get a positive diagnosis for a genetic disorder it provides a sense of direction to the patient and their family since they know what to expect in the future.”
Dr. Sanchez believes physicians truly benefit from WGS since it covers more aspects of genetic testing compared to sending patients for multiple “standard” genetic tests. He feels the standard approach is fine if you are able to look in the right places, but rare diseases often do not provide clues as to where to start looking. The process can then become compartmentalized and can lead clinicians astray.
It is time to get away from utilizing whole genome sequencing as a last-ditch “Hail Mary” football pass type effort to find out what is wrong with a patient. It should become the first play in the playbook for diagnosis if genetics are involved. By doing so, whole genome testing can become the saving grace for families facing the trauma of the unknown.
“When patients receive a positive result from whole genome sequencing testing it provides peace of mind to a family since they can understand why symptoms are occurring and what they can do to treat the disorder,” Dr. Sanchez said. “With WGS, physicians always have the possibility of going back and re-analyzing results to get an even better understanding of the diagnosis.”
The ability to re-analyze results comes about because, unlike with other technologies, whole genome sequencing does not require that individual genes be isolated and amplified prior to sequencing. Instead, the entire DNA is sequenced and then sophisticated algorithms are applied via software to enable examination and ranking of variants according to the severity of the effect of the variant on genes that most closely match the patient’s clinical symptoms.
Those results are then parsed based on the known inheritance patterns of these genes. This analysis process can be repeated at any time, incorporating new findings from the ever-expanding medical literature or taking into account new clinical symptoms developed by the patient that may provide greater insight into diagnosis or treatment options.
A long and drawn-out process for families or individuals in regards to genetic testing does not have to exist anymore. WGS provides clarity for genetic diseases through sophisticated biometrics and comprehensive evaluation that is tailored to the individual based on their clinical symptoms – not dictated by genes selected prior to sequencing. This is all accomplished from a single sample that can be saved for future analysis, if necessary. The technology to drastically shorten a costly and cumbersome process with a single sample and test is readily available. It is time to embrace it.
Haim Neerman is a co-founder and CEO of Variantyx, a company that uses Whole Genome Sequencing to test for genetic disorders.
