For individuals grappling with rare and enigmatic medical symptoms, receiving a diagnosis is frequently a prolonged and exasperating journey characterized by numerous tests and limited answers. The Washington University School of Medicine in St. Louis Undiagnosed Diseases Network (UDN) Diagnostic Center of Excellence was formed in 2019 to unravel the most challenging medical enigmas in Missouri and surrounding states. It operates as one of 11 locations in the national UDN, supported by the National Institutes of Health (NIH). Over the past five years, the center’s collective team of WashU Medicine geneticists, bioinformaticists, and specialists in pediatric and adult medicine have addressed 189 such cases, successfully solving 56 of them, achieving a success rate comparable to the national network.
The center is now poised for growth. Energized by the renewal of its five-year $3.8 million grant, the UDN leadership intends to enhance outreach to communities with limited medical resources and expand its capacity from 30 to 50 patients annually. A partnership has been formed with the St. Louis Integrated Health Network, an organization focused on enhancing the quality, accessibility, and cost-effectiveness of health care. Together, they will identify individuals with obscure conditions in underserved communities who may benefit from the center’s advanced diagnostic services, thereby aiding their access to such services.
As most rare and obscure conditions possess a genetic aspect, genetic testing is a crucial element of the UDN’s methodology, complemented by comprehensive evaluations from WashU Medicine pediatricians and other specialists skilled in rare disorders. Occasionally, a genetic alteration is detected, but its significance remains ambiguous. In such instances, UDN researchers employ simple organisms—specifically, nematode worms (C. elegans) and zebrafish—to investigate the ramifications of the genetic change and determine if it is likely responsible for the patient’s symptoms.
Each case is distinct and intricate, sometimes requiring months or even years to resolve. Securing a diagnosis can be crucial in directing care decisions, establishing qualification for precision medicine treatments and clinical trials, and linking patients and their families with communities of others facing similar challenges. In some instances, the diagnostic journey may conclude without a clear answer, leaving patients and physicians feeling frustrated and disheartened, yet at least the patient and their family can take solace in knowing that every possible effort has been made to provide them with clarity.
Eliminating barriers to genetic testing
Approximately 3 million individuals in the U.S. contend with undiagnosed diseases, described as medical conditions lacking a recognized cause despite extensive investigations. Members of medically underserved communities—typically low-income areas with a scarcity of primary care providers and limited access to healthcare—struggle considerably to attain a diagnosis.
One contributing factor is that the majority of undiagnosed diseases are likely of genetic nature. Genetic testing can be costly—ranging from several hundred dollars to over $5,000, contingent on the specific test—and may not always be reimbursed by insurance. Research has demonstrated that uninsured or underinsured individuals have decreased access to genetic testing.
“A patient’s insurance situation is a significant element impacting whether they are referred for and receive genetic testing,” explained Brett Maricque, PhD, an assistant professor of genetics at WashU Medicine and the head of the center’s community engagement team. “The location where they receive care is equally important. Community health clinics often have limited financial means to cover genetic testing. Thus, our focus has shifted to increasing access to cutting-edge diagnostics, especially for those who are underinsured or uninsured.”
Research has also indicated that genetic disorders are less likely to be identified and accurately diagnosed among individuals of color. This is partially because genetic test results are benchmarked against reference databases to ascertain their significance, which predominantly includes individuals of European descent, leading to a likelihood that individuals from other ancestral backgrounds may receive inconclusive findings.
Keeping these challenges in mind—alongside encouragement from the national UDN—director Patricia Dickson, MD, the Centennial Professor of Pediatrics and a professor of genetics at WashU Medicine, evaluated the demographic makeup of the center’s patient base.
“We handle the most challenging cases,” Dickson stated. “These individuals have spent years searching in vain for a diagnosis. While we don’t always find answers, every person deserves the opportunity for resolution. That opportunity should not be dictated by one’s identity, place of residence, or financial means.”
The evaluation indicated that the ratio of rural patients among those served by the center was consistent with the demographics of the surrounding regions; however, the proportions related to race, ethnicity, and income levels were not. The center’s patient population exhibited an underrepresentation of Black and Hispanic individuals alongside those from lower-income backgrounds.
It was Maricque who proposed partnering with the Integrated Health Network to tackle the disparities within the patient demographic. The Integrated Health Network synchronizes the efforts of the four Federally Qualified Health Centers in the St. Louis area, which are government-supported nonprofit clinics providing primary care in underserved neighborhoods.
“Our primary aim is to enhance healthcare access for individuals in marginalized communities,” stated Brittany Jones, the assistant director of clinical and community services and racial equity initiatives at the Integrated Health Network. “For many, maneuvering through the healthcare system just to schedule a physical, obtain vaccinations, or receive prescriptions can be a daunting task, and it becomes even more complicated when they are dealing with an obscure condition. Many are unaware of what undiagnosed diseases entail or lack a clear pathway toward receiving a diagnosis. They may struggle to articulate their symptoms in a manner that healthcare providers grasp, and practitioners do not always allow adequate time and space to address patients’ needs, concerns, or objectives. Our role is to bridge that divide to ensure that everyone receives the care they require and deserve.”
A portion of the center’s renewed grant will be designated for a full-time position within the Integrated Health Network, dedicated to assisting individuals with undiagnosed diseases in accessing healthcare. This individual will work to raise public awareness about undiagnosed diseases, aid healthcare providers in improving their communication skills to minimize misunderstandings, and assist patients in navigating the complexities of healthcare systems.
and assist in referrals to the WashU Medicine UDN center.
“Our aim is to align our participant demographics with the demographics of our region, not by rejecting anyone, but by enhancing our efforts to identify individuals who could gain from our services in communities that we currently do not serve effectively,” Dickson stated. “We are lucky to have a collaborator in the Integrated Health Network that understands how to sensitively reach out to communities and involve them. I am enthusiastic about collaborating with them to integrate this program more entirely into the St. Louis community.”
About Washington University School of Medicine
WashU Medicine stands as a worldwide authority in academic medicine, encompassing biomedical research, patient care, and educational initiatives with a faculty of 2,900. Its portfolio of research funding from the National Institutes of Health (NIH) ranks second among U.S. medical schools and has seen a growth of 56% over the past seven years. In conjunction with institutional investment, WashU Medicine dedicates over $1 billion each year to innovation and education in both basic and clinical research. Its faculty practice consistently ranks among the top five nationwide, with over 1,900 physicians practicing across 130 sites and serving as the medical staff for Barnes-Jewish and St. Louis Children’s hospitals affiliated with BJC HealthCare. WashU Medicine has a renowned history in MD/PhD training, recently allocating $100 million towards scholarships and curriculum enhancement for its medical students, and hosts exceptional training initiatives in every medical subspecialty, in addition to physical therapy, occupational therapy, and audiology and communication sciences.
Initially published on the WashU Medicine website
The article Undiagnosed diseases clinic expands outreach to underserved communities was first featured on The Source.