The overwhelming majority of rare diseases have a genetic origin, with estimates varying from 71.9% to 80% of rare diseases. Although a rare disease is defined as a condition that affects fewer than 200,000 people domestically, collectively, rare diseases impact approximately 30 million US residents, with at least one of the more than 7,000 rare genetic disorders. In fact, the population of patients with at least one rare disease mirrors the prevalence of people who have type 2 diabetes, or one in every 10 people. Despite their prevalence, most rare conditions are treated only when symptomatic, as many cases remain either misdiagnosed or undiagnosed. As with most health conditions, it is imperative to have a prompt and accurate diagnosis to improve outcomes and avoid inappropriate or unnecessary treatments that may pose severe side effects to the patient.
To that end, this report weighs the less obvious pros and cons of genetic testing in rare diseases of which neurologists should be aware.
The Path to Accurate Diagnosis Remains Long Despite Increased Genetic Testing
When it comes to identifying the greatest challenge in rare genetic disease testing for the neurology community, experts have different opinions. For Kiley Boone Quintana, MD, assistant professor of pediatrics at the University of New Mexico in Albuquerque, the greatest challenge for neurologists navigating this space lies in becoming comfortable with the unknown.
“Many neurologists think genetic testing will certainly find an answer or that the answers will be black and white — which is not true,” said Dr. Quintana. “Instead of clear answers, we often find variants of unknown significance and genetic changes like a deletion or duplication that can have reduced penetrance, so clinicians have to become comfortable with not always having an answer or not knowing exactly how the answer will impact the person.”
Dr. Kiley Boone Quintana
One reason for late diagnosis is the need for more knowledge or familiarity a clinician may have with a certain disease, given its rarity.
Perhaps the nebulous nature of genetic testing for people living with rare diseases unveils another drawback, which centers around what researchers refer to as the “diagnostic odyssey.” While the concept describing the average time to diagnosis as 5 years, the time to diagnosis can vary greatly in the rare disease community. In some cases, patients may experience diagnostic delays of only a few months. For others, the time frame could be a decade or greater. The time frame often depends on the patient’s age, phenotype, and accessibility to resources.
Despite these diagnostic challenges, Debra Regier, MD, PhD, chief, genetics and metabolism, at Children’s National Hospital in Washington, DC, sees the silver lining in identifying the underlying cause of a patient’s symptoms of illness. In some cases, a diagnosis leads a patient to access disease-specific medication. However, in the rare genetic disease space, the occurrence is low, as only approximately 10% of these diagnosed conditions have an available treatment.
Despite the small selection of disease-specific therapies for this patient population, patients may still have options, especially when it comes to palliating symptoms.
Dr. Debra Regier
“We often look toward disease experts to consider what medications are more likely to be supportive,” Dr. Regier said. “This might mean considering a pain regimen, a seizure regimen, other type of symptomatic treatment, or even using some information learned to support the current patient from cases where other families may have preceded them in the odyssey.”