Imagine waking up each day in pain, but every doctor describes your test results as normal. They send you home, again and again, with no answers. Millions of people around the world face this frustrating reality. Rare and undiagnosed diseases often leave patients misunderstood, misdiagnosed, and untreated for years.
A Long and Winding Road
Despite advances in medical science, an estimated 350 million people globally experience the impact of rare diseases. Yet, the average time to diagnosis is five to seven years, with some patients never receiving one at all. This prolonged journey — often called the diagnostic odyssey — highlights a major gap in modern medicine.
Most patients with undiagnosed or rare diseases visit multiple specialists, undergo repeated invasive tests, and receive conflicting diagnoses. In many cases, symptoms do not conform to textbook presentations, leading to confusion among healthcare providers.
One key reason for these delays is the limited awareness and education about rare diseases. Medical professionals receive training in how to recognize common diseases, and medical schools often overlook what we call “zebra” diagnoses in favor of more familiar conditions. This approach, while practical, works to the detriment of patients whose diseases lie outside the mainstream.
In addition, many rare diseases have genetic origins, but standard screening panels do not always include them. Doctors may have very little familiarity with newly identified conditions, ultra-rare ones, or those that have no known genetic markers. The lack of diagnostic tools — particularly in resource-limited settings — only compounds the problem.
Bittersweet Diagnosis
The journey to a diagnosis comprises medical, emotional, and financial challenges. Doctors may brush off patients, telling them that their condition is “all in their head,” and so rare disease sufferers experience stigma, dismissal, or even accusations of malingering. For parents of affected children, the quest for answers often becomes a full-time job that involves advocacy, travel, and immense psychological stress.
Consider the case of Ava, a seven-year-old girl in the United States who began experiencing seizures, developmental delays, and unusual skin pigmentation. Her parents visited pediatricians, neurologists, dermatologists, and geneticists. Some doctors suggested autism as the cause of her symptoms; others proposed mitochondrial disorders; and no one could offer certainty.
After five years, Ava finally received a diagnosis of a newly characterized neurocutaneous syndrome through a research program at a major academic hospital. The diagnosis brought relief but also the realization that no cure or established treatment exists. Still, having a name for her condition opened doors to support groups, to research trials, and, crucially, to emotional validation.
Without a diagnosis, patients often lack access to treatment plans, insurance coverage, disability support, or clinical trials. They can face exclusion from research, medical record systems, and public health statistics.
They may also suffer a profound emotional toll. Studies show that patients with undiagnosed conditions experience higher levels of depression, anxiety, and social isolation. For many, the validation of a diagnosis — even without a cure — can transform their quality of life.
The Role of Research and Genomics
Recent advancements in whole exome and genome sequencing, along with multi-omics approaches, have opened new pathways for diagnosing complex and ultra-rare conditions. Programs like the NIH Undiagnosed Diseases Network in the United States, and similar initiatives in Europe and Asia, aim to provide diagnoses where others have failed.
These programs often use a multidisciplinary approach that combines clinical expertise, genomic data, and bioinformatics to uncover novel diseases. In some cases, researchers even name newly discovered syndromes after the patients who first present them.
Still, patients do not have equal access to such advanced diagnostics, and many people in developing countries may never benefit from these innovations. Solving the challenge of undiagnosed diseases around the world requires systemic change with the following characteristics:
- Medical Education Reform: Clinicians need better training on rare diseases and on how to handle diagnostic uncertainty.
- Cross-Border Data Sharing: Global collaboration can accelerate identification of rare syndromes by pooling patient data.
- Patient-Led Advocacy: Groups like the Rare Disease Foundation and the National Organization for Rare Disorders can empower patients to become research partners and advocates.
- Ethical Use of AI: Machine learning, if implemented responsibly, can analyze complex symptom patterns and genomic data to detect rare conditions earlier.
- Expanded Newborn Screening: Testing that includes more conditions can reduce delays in diagnosis and help treat patients from infancy on.
Rare and undiagnosed diseases represent more than medical mysteries: They embody deep, human stories of perseverance, frustration, and hope. As health-care systems worldwide strive for equity and precision, they must not forget those whose suffering remains unnamed.
Finding a diagnosis shouldn’t be a luxury or a miracle. It should be a basic right — one that affirms a patient’s pain, unlocks care, and opens the door to healing.
Behnaz Akbari received her BS in chemistry and MSc in analytical chemistry in Iran, where she developed a chromatography method for detecting a biomarker of oxidative stress in human serum samples. She worked at Newcastle University (UK) in f luorescence probes to establish a photochemical platform within ROS-mediated DNA lesions (e.g., 8-oxodG). She then came to the U.S. and received her second MSc in chemistry from the University of Nebraska-Lincoln and a third MSc in bioimaging from the Boston University School of Medicine. She has received awards and grants from the National Organization for Rare Disorders (NORD), Stanford University School of Medicine, and Purdue University. She was recognized as among the Top 10 Most-Cited Papers from Wiley in 2024 and 2025.
This article was originally published in AWIS Magazine. Join AWIS to access the full issue of AWIS Magazine and more member benefits.