This App Helps Diagnose Rare Genetic Disorders from a Picture
FDNA's Face2Gene technology analyzes patient biometric data using artificial intelligence, identifying correlations with disease-causing genetic variations.
Medical geneticist Omar Abdul-Rahman had a hunch. He thought that the three-year-old boy with deep-set eyes, a rounded nose, and uplifted earlobes might have Mowat-Wilson syndrome, but he'd never seen a patient with the rare disorder before.
"If it weren't for the app I'm not sure I would have had the confidence to say 'yes you should spend $1000 on this test."
Rahman had already ordered genetic tests for three different conditions without any luck, and he didn't want to cost the family any more money—or hope—if he wasn't sure of the diagnosis. So he took a picture of the boy and uploaded the photo to Face2Gene, a diagnostic aid for rare genetic disorders. Sure enough, Mowat-Wilson came up as a potential match. The family agreed to one final genetic test, which was positive for the syndrome.
"If it weren't for the app I'm not sure I would have had the confidence to say 'yes you should spend $1000 on this test,'" says Rahman, who is now the director of Genetic Medicine at the University of Nebraska Medical Center, but saw the boy when he was in the Department of Pediatrics at the University of Mississippi Medical Center in 2012.
"Families who are dealing with undiagnosed diseases never know what's going to come around the corner, what other organ system might be a problem next week," Rahman says. With a diagnosis, "You don't have to wait for the other shoe to drop because now you know the extent of the condition."
A diagnosis is the first and most important step for patients to attain medical care. Disease prognosis, treatment plans, and emotional coping all stem from this critical phase. But diagnosis can also be the trickiest part of the process, particularly for rare disorders. According to one European survey, 40 percent of rare diseases are initially misdiagnosed.
Healthcare professionals and medical technology companies hope that facial recognition software will help prevent families from facing difficult disruptions due to misdiagnoses.
"Patients with rare diseases or genetic disorders go through a long period of diagnostic odyssey, and just putting a name to a syndrome or finding a diagnosis can be very helpful and relieve a lot of tension for the family," says Dekel Gelbman, CEO of FDNA.
Consequently, a misdiagnosis can be devastating for families. Money and time may have been wasted on fruitless treatments, while opportunities for potentially helpful therapies or clinical trials were missed. Parents led down the wrong path must change their expectations of their child's long-term prognosis and care. In addition, they may be misinformed regarding future decisions about family planning.
Healthcare professionals and medical technology companies hope that facial recognition software will help prevent families from facing these difficult disruptions by improving the accuracy and ease of diagnosing genetic disorders. Traditionally, doctors diagnose these types of conditions by identifying unique patterns of facial features, a practice called dysmorphology. Trained physicians can read a child's face like a map and detect any abnormal ridges or plateaus—wide-set eyes, broad forehead, flat nose, rotated ears—that, combined with other symptoms such as intellectual disability or abnormal height and weight, signify a specific genetic disorder.
These morphological changes can be subtle, though, and often only specialized medical geneticists are able to detect and interpret these facial clues. What's more, some genetic disorders are so rare that even a specialist may not have encountered it before, much less a general practitioner. Diagnosing rare conditions has improved thanks to genomic testing that can confirm (or refute) a doctor's suspicion. Yet with thousands of variants in each person's genome, identifying the culprit mutation or deletion can be extremely difficult if you don't know what you're looking for.
Facial recognition technology is trying to take some of the guesswork out of this process. Software such as the Face2Gene app use machine learning to compare a picture of a patient against images of thousands of disorders and come back with suggestions of possible diagnoses.
"This is a classic field for artificial intelligence because no human being can really have enough knowledge and enough experience to be able to do this for thousands of different disorders."
"When we met a geneticist for the first time we were pretty blown away with the fact that they actually use their own human pattern recognition" to diagnose patients, says Gelbman. "This is a classic field for AI [artificial intelligence], for machine learning because no human being can really have enough knowledge and enough experience to be able to do this for thousands of different disorders."
When a physician uploads a photo to the app, they are given a list of different diagnostic suggestions, each with a heat map to indicate how similar the facial features are to a classic representation of the syndrome. The physician can hone the suggestions by adding in other symptoms or family history. Gelbman emphasized that the app is a "search and reference tool" and should not "be used to diagnose or treat medical conditions." It is not approved by the FDA as a diagnostic.
"As a tool, we've all been waiting for this, something that can help everyone," says Julian Martinez-Agosto, an associate professor in human genetics and pediatrics at UCLA. He sees the greatest benefit of facial recognition technology in its ability to empower non-specialists to make a diagnosis. Many areas, including rural communities or resource-poor countries, do not have access to either medical geneticists trained in these types of diagnostics or genomic screens. Apps like Face2Gene can help guide a general practitioner or flag diseases they might not be familiar with.
One concern is that most textbook images of genetic disorders come from the West, so the "classic" face of a condition is often a child of European descent.
Maximilian Muenke, a senior investigator at the National Human Genome Research Institute (NHGRI), agrees that in many countries, facial recognition programs could be the only way for a doctor to make a diagnosis.
"There are only geneticists in countries like the U.S., Canada, Europe, Japan. In most countries, geneticists don't exist at all," Muenke says. "In Nigeria, the most populous country in all of Africa with 160 million people, there's not a single clinical geneticist. So in a country like that, facial recognition programs will be sought after and will be extremely useful to help make a diagnosis to the non-geneticists."
One concern about providing this type of technology to a global population is that most textbook images of genetic disorders come from the West, so the "classic" face of a condition is often a child of European descent. However, the defining facial features of some of these disorders manifest differently across ethnicities, leaving clinicians from other geographic regions at a disadvantage.
"Every syndrome is either more easy or more difficult to detect in people from different geographic backgrounds," explains Muenke. For example, "in some countries of Southeast Asia, the eyes are slanted upward, and that happens to be one of the findings that occurs mostly with children with Down Syndrome. So then it might be more difficult for some individuals to recognize Down Syndrome in children from Southeast Asia."
There is a risk that providing this type of diagnostic information online will lead to parents trying to classify their own children.
To combat this issue, Muenke helped develop the Atlas of Human Malformation Syndromes, a database that incorporates descriptions and pictures of patients from every continent. By providing examples of rare genetic disorders in children from outside of the United States and Europe, Muenke hopes to provide clinicians with a better understanding of what to look for in each condition, regardless of where they practice.
There is a risk that providing this type of diagnostic information online will lead to parents trying to classify their own children. Face2Gene is free to download in the app store, although users must be authenticated by the company as a healthcare professional before they can access the database. The NHGRI Atlas can be accessed by anyone through their website. However, Martinez and Muenke say parents already use Google and WebMD to look up their child's symptoms; facial recognition programs and databases are just an extension of that trend. In fact, Martinez says, "Empowering families is another way to facilitate access to care. Some families live in rural areas and have no access to geneticists. If they can use software to get a diagnosis and then contact someone at a large hospital, it can help facilitate the process."
Martinez also says the app could go further by providing greater transparency about how the program makes its assessments. Giving clinicians feedback about why a diagnosis fits certain facial features would offer a valuable teaching opportunity in addition to a diagnostic aid.
Both Martinez and Muenke think the technology is an innovation that could vastly benefit patients. "In the beginning, I was quite skeptical and I could not believe that a machine could replace a human," says Muenke. "However, I am a convert that it actually can help tremendously in making a diagnosis. I think there is a place for facial recognition programs, and I am a firm believer that this will spread over the next five years."
Urinary tract infections account for more than 8 million trips to the doctor each year.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
A surgeon at Massachusetts General Hospital prepares a pig organ for transplant.
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.