Science1 publisher3 min readPublished
Wider genetic testing could cut the five-to-seven-year wait for a rare-disease diagnosis
Rare-disease specialists told Live Science that wide genetic testing could diagnose most rare diseases, since about 80% of them are genetic in origin. That share counts diseases, not patients, so it sets a ceiling on what sequencing can reach for the people still searching.
The Scientist · Science desk
What happened
- On average, people with rare diseases spend five to seven years searching and see 12 specialists before they receive a diagnosis.
- An estimated 30 million-plus people in the United States live with a rare or undiagnosed disease, according to Live Science.
- Clinicians often cannot link a patient's symptoms to one condition, so patients collect several separate diagnoses over time.
- Kelly Kemper has spent five years seeking an explanation for her son's rare form of dystonia, and he still has no diagnosis.
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Why it matters
- constraint Patients sequenced today can come back without a match when their disease is among the hundreds still to be described over the next few years.
- exposure Until sequencing moves earlier, patients keep taking treatments chosen without a diagnosis, and Hamosh puts the chance that any one prescription hurts at one in three.
- decision Health systems deciding whether to sequence before the specialist rounds need to know how many of the roughly 8,000 genetic rare diseases already have a known cause.
Emily Glanton, a genetic counselor and associate director at the data coordinating center for the National Institutes of Health's Undiagnosed Diseases Network, gave Live Science the 80% figure [9]. Researchers have documented more than 10,000 rare diseases, each affecting fewer than 200,000 people in the United States [6][17]. At 80%, roughly 8,000 or more of them have a genetic origin [3]. The figure does not show how patients are spread across those conditions, so a genetic majority of diseases need not be a genetic majority of people. The other 20% trace to environmental causes such as a toxin exposure or a viral infection [9].
The list is still growing. Dr. Ada Hamosh, a geneticist who directs the Johns Hopkins Medicine-Kennedy Krieger Institute NORD Rare Disease Centers of Excellence Network, said about 250 new rare diseases are discovered each year [1][7]. Against the documented total, that is roughly 2.5% a year [1]. Jacqueline Harris, a pediatric neurologist who directs Kennedy Krieger's Epigenetics Clinic in Baltimore, told Live Science there is no way to know exactly how many people "have a disease that we haven't even discovered the name or cause of" [11].
Live Science reports that emerging data suggests genetic testing could speed diagnosis, and that the specialists it interviewed expect wide use to help diagnose the majority of rare diseases [4]. The article does not cite a diagnostic yield or compare time to diagnosis with and without sequencing. On this evidence, I think the claim holds for genetic diseases whose cause has already been described. "Now, with the wide availability of vast, somewhat inexpensive, genetic testing and whole genome sequencing available, we're really at the point of understanding a lot more about these rare and ultra-rare diseases," said Danielle Carnival, chief executive of the Undiagnosed Diseases Network Foundation [5]. "And then hopefully, that turns into the ability to treat them," she said [19].
Waiting has a cost of its own. Twelve specialists across five to seven years works out to a new specialist every five to seven months [4]. Along the way, patients may be given incorrect, ineffective or even harmful treatments [3]. "Any medicine that you prescribe has a one-third chance of working, a one-third chance of doing nothing, and a one-third chance of hurting you," Hamosh said [12]. Fewer than 5% of documented rare diseases have an FDA-approved treatment [6]. Hamosh still argued for the diagnosis itself: "I do not want to understate this: The right diagnosis is unbelievably powerful, even if you can't do something." [13]
Kelly Kemper, who sits on the foundation's patient advisory council, said undiagnosed patients often "end up with a little bit of a diagnosis" [14]. "We are the only people who are consistently praying for positive test results," she told Live Science [15].
What to watch
- Diagnostic-yield figures for whole genome sequencing in long-undiagnosed patients would show how much of the 80% genetic share testing can reach today.
- A measured drop in the five-to-seven-year average in health systems that sequence patients before the specialist rounds.
- Whether the pace of about 250 newly described rare diseases a year rises as sequencing spreads.