In this four-part series, we examine the various challenges faced by patients and families affected by rare diseases. We also interview clinicians, researchers, and the advocacy community at large to understand their perspectives on bottlenecks in rare disease diagnosis and treatment.
Part IV of the series discusses the shortage of genetics specialists, limited medical knowledge, and the challenge of integrating extensive information.
Today, the genetics workforce is far outnumbered by the volume of patients who need to see a geneticist, and this shortage is further exacerbated by the increasing number of genetic diagnoses being made.
“We figured out that there is roughly one geneticist for every 600,000 or so people in the United States, and in particular this is a challenge for adults, as only 6% of geneticists work in adult departments,” geneticists at Washington University in St. Louis said. “We absolutely need to train more medical geneticists, particularly adult geneticists, and we need to train more genetic counselors.”
Leslie Biesecker, Chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health, agreed.
“We need to integrate genetics and genomics training into primary care and subspecialty education to ensure that the entire physician workforce is taking advantage of these powerful tools for patient care,” Biesecker said. “We need to have clinicians who understand what this testing is and what it is not and communicate that clearly and simply to the patient.”
As Biesecker puts it, clinicians should not hesitate to take advantage of genetic testing.
“Don’t be afraid to use it – it is like many other powerful medical tools, both highly useful and associated with some risks,” Biesecker said. “Many clinicians and families think it is too complex for them to understand. In the end, it is just a test and can be explained and understood by both primary care clinicians and families.”
Although the clinician mindset and discomforts of pushing for Next Generation Sequencing at the outset are challenges, Biesecker believes these attitudes ultimately stem from the lack of change occurring in clinical practice.
“There are a lot of advances that have occurred in the past 10 or so years that should have completely changed practice, but has not,” said Biesecker, who is also a trained clinical and molecular geneticist. “A great example is rare disease – any individual who has symptoms or manifestations even moderately to be caused by a gene variant should be sequenced at the beginning of the diagnostic process. There is a legacy that we are up against that leads clinicians to believe that something like a clinical exome or clinical genome test should be a test of last resort. I disagree.”
Limited Medical Knowledge and the Attempt to Integrate all Information
For almost 70% of human genes, there is no known phenotype or disease associated with them, according to geneticists at Washington University in St. Louis. Furthermore, for some undiagnosed patients, their condition may arise from a disease that has not been previously described.
“The biggest challenge today in genomic medicine is really trying to figure out what to do with the large amount of information and data that we collect both from a diagnostic standpoint and ultimately from a therapeutic standpoint,” geneticists at Washington University in St. Louis said. “There’s a misconception that if you’re looking at all the genes, you should be able to immediately know whether someone does or does not have a particular problem. But everybody’s DNA is a little bit different.”
As the technology improves in a way that enhances detection, the geneticists said that it becomes increasingly difficult to interpret variants in the sequencing, as it is sometimes unclear if the mutation is causing the problem or simply making the patient unique.
“We’re still at the beginning of trying to figure out how to interpret the findings that we get in our genetic sequencing studies,” they said. “On top of that, we are discovering that the sequence isn’t everything. There are rearrangements and modifications to genes that don’t affect the sequence and that some of our tests don’t do a good job of finding. We are very much on a rapid upslope.”
Michele Herndon says the biggest take-away from her involvement in her son’s rare disease journey is that “people really are stronger than they think and can endure a lot and still thrive given the right circumstances.”
“We have been helped by and supported by amazing physicians, therapists, and other health care providers,” Michele said. “My son currently lives with us but is planning on moving back to the dorm at Saint Louis University in the fall with the help of a few personal care attendants. He is thankful that this disease so far has not affected his intelligence at all and he is still completely mentally intact. He is learning how to be as independent as possible, despite his physical limitations.”
York believes the rare disease community has made significant strides in areas including research, patient focused drug development, access to care, and resource allocation for patients, while research investigators like Biesecker are excited about the possibilities that lie ahead in the field of genomics.
“In basic genomics I am extremely excited about studies of the three-dimensional topology of the genome,” Biesecker said. “I think this basic research will illuminate regulatory functions that are desperate to identify and this will in turn lead to increased diagnostic opportunities in clinical genomics.”
Though many of the current challenges are thinking about how to use genetic sequencing to diagnose rare disease, Biesecker is looking ahead to when sequencing will be used to prevent disease before the affected individual even recognizes that he or she is ill, stating that “this is the promise of preventive, personalized genomic medicine.”
According to RG Founder and President Jimmy Lin, RG is looking into the newest innovations beyond genome sequencing.
“[This] includes deeper phenotyping through wearables and other monitoring devices as well as leveraging machine learning to intersect genomic data with medical data, patient-reported data, among others," Lin said. "This is an exciting time for health field in general and we are hoping to bring these technologies to the rare disease population."
Throughout the 10 years she has been in practice, Cincinnati Children’s Hospital clinical geneticist Loren Peña believes that clinical genetics is evolving as a specialty from being diagnostically focused to treatment oriented.
“There has been an explosion of potential treatments of rare disorders,” Peña said. “No disease is too rare to have a treatment developed for it, and I think there’s a lot of hope for families dealing with rare diseases.”
Author Bio: Lauren Fang is a patient advocate associate for Rare Genomics Institute. She is finishing her last year of undergraduate studies in biomedical engineering at Johns Hopkins University. Lauren is interested in global health, medical devices, and genomics research and is deciding what she would like to study in graduate school.