This App Helps Diagnose Rare Genetic Disorders from a Picture
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."
In 1962, the world was a remarkably different place: Neil Armstrong had yet to take his first steps on the lunar surface, John F. Kennedy was serving as president of the United States, and the Beatles were still a few years away from superstardom, having just recorded their first single.
The word “measles” was also a household name. Measles, which still exists in parts of the world today, is a highly contagious viral infection that typically causes fever, cough, muscle pain, fatigue, and a distinctive red rash. Measles was so pervasive around the world in 1962 that most children had gotten sick with it before the age of fifteen—but even though it was common, it was far from harmless. Measles killed around 400 to 500 people per year in the United States, and approximately 2.6 million people each year worldwide. Countless others suffered severe complications from measles, such as permanent blindness.
Tragedy hits home
Author Roald Dahl at his Buckinghamshire home with Olivia, daughter Chantal, and wife Patricia Neal in 1960.
Ben Martin / Getty Images
That year, British author Roald Dahl was beginning to make a name for himself, having just published his best-selling book James and the Giant Peach. Dahl, who would go on to write some of the most well-loved children’s books of the century, lived in southern England with his wife and three children. One day, Dahl and his wife, actress Patricia Neal, received word that there was an outbreak of measles at his daughters’ school.
While some parents quarantined their children, many others also considered measles a harmless childhood disease. Neal later recalled in her autobiography that a family member had advised her to “let the girls get measles,” thinking it would strengthen their immune systems and be “good for them.” Reluctantly, Dahl and Neal let their two school-aged children, Olivia and Chantal, continue school. Olivia, then aged seven, fell sick with the measles not long after that.
Neither Dahl nor Neal were terribly concerned about Olivia’s infection. Dahl would write later that it seemed to be taking its “usual course,” and the two would read and spend time together while Olivia rested. After a few days of fever and fatigue, Dahl wrote, Olivia seemed like she was “well on the road to recovery.”
But one afternoon, as the two sat on Olivia’s bed making animals out of pipe cleaners, Dahl noticed that Olivia’s “fingers and her mind were not working together.” When Dahl asked how she was feeling, Olivia replied, “I feel all sleepy.”
Within an hour, Dahl wrote, Olivia was unconscious. Within 12 hours, she was dead.
Olivia died of measles encephalitis, an inflammation of the brain caused by an infection. Approximately 1 in 1,000 people infected with measles develop encephalitis, and of those who develop it, between 10 and 20 percent will die.
Dahl was overcome with grief and wracked with guilt for being unable to prevent his daughter’s death. Mourning, Dahl threw himself into his writing and, in his spare time, spent hours lovingly constructing a rock garden on Olivia’s grave in a local churchyard.
After Olivia’s death, Dahl wrote sixteen novels and several collections of short stories, including Matilda, Fantastic Mr. Fox, and Willy Wonka and the Chocolate Factory, which garnered him worldwide acclaim. His most influential piece of writing, however, wasn’t written until 1986.
A father's plea
Roald Dahl and the open letter he wrote in 1986, encouraging parents to vaccinate their children against measles.
By 1986, measles was no longer the global health threat that it had been in the 1960s, thanks to a measles vaccine that became available just one year after Olivia had died. Still, in the United Kingdom alone, approximately 80,000 people every year were infected with measles. This bothered Dahl, especially since measles rates in the United States had dropped by 98 percent compared to pre-vaccine years. “Why do we have so much measles in Britain when the Americans have virtually gotten rid of it?,” Dahl was reported to have said.
So Dahl set out to prevent a tragedy like Olivia’s from happening again. With encouragement from several prominent public health activists, Dahl wrote an open letter addressed to parents in the UK. The letter recounted his daughter’s death from encephalitis and begged parents to protect their own children from measles:
“...there is today something that parents can do to make sure that this sort of tragedy does not happen to a child of theirs. They can insist that their child is immunised [sic] against measles. I was unable to do that for Olivia in 1962 because in those days a reliable measles vaccine had not been discovered. Today a good and safe vaccine is available to every family and all you have to do is to ask your doctor to administer it.”
Dahl went on to say that although many parents still viewed measles as a harmless illness, he knew from experience that it was not. Measles was capable of causing disability and death, Dahl wrote, whereas a child had a better chance of “choking on a chocolate bar” than developing any serious complication from the vaccine. Dahl ended his letter by saying how happy he knew Olivia would be “if only she could know that her death had helped to save a good deal of illness and death among other children.”
Dahl’s letter was published in early 1986 and distributed to local healthcare workers, schools, and to parents of children who were particularly at risk. As the letter circulated, vaccination rates continued to climb year after year.
Thirty-one years after Dahl’s letter was published, and 55 years after Olivia’s death, the World Health Organization declared in 2017 that measles had officially been eradicated for the first time in the UK thanks to high rates of vaccination.
A small step back
As vaccination rates decline, measles is now making a strong comeback in the United States and elsewhere.
Today, vaccination rates for the measles are in decline, and countries like the UK and the US, who had once eradicated measles completely, are now seeing a comeback. The Centers for Disease Control and Prevention (CDC) recently reported that between December 1, 2023 and January 23, 2024, 23 cases of measles had been confirmed across multiple states. The majority of these cases, they reported, were among children and adolescents who had traveled internationally and had not yet been vaccinated even though they were eligible to do so.
Roald Dahl passed away in 1990, but fortunately, his writing continues to live on. While readers can explore fantastical worlds through his novels and short stories, they can also look back to a reality when tragic deaths like Olivia’s happened far too often. The difference is that today, thanks to modern science, we now have the tools to stop them.
Sarah Watts is a health and science writer based in Chicago.
On today’s episode of Making Sense of Science, I’m honored to be joined by Dr. Paul Song, a physician, oncologist, progressive activist and biotech chief medical officer. Through his company, NKGen Biotech, Dr. Song is leveraging the power of patients’ own immune systems by supercharging the body’s natural killer cells to make new treatments for Alzheimer’s and cancer.
Whereas other treatments for Alzheimer’s focus directly on reducing the build-up of proteins in the brain such as amyloid and tau in patients will mild cognitive impairment, NKGen is seeking to help patients that much of the rest of the medical community has written off as hopeless cases, those with late stage Alzheimer’s. And in small studies, NKGen has shown remarkable results, even improvement in the symptoms of people with these very progressed forms of Alzheimer’s, above and beyond slowing down the disease.
In the realm of cancer, Dr. Song is similarly setting his sights on another group of patients for whom treatment options are few and far between: people with solid tumors. Whereas some gradual progress has been made in treating blood cancers such as certain leukemias in past few decades, solid tumors have been even more of a challenge. But Dr. Song’s approach of using natural killer cells to treat solid tumors is promising. You may have heard of CAR-T, which uses genetic engineering to introduce cells into the body that have a particular function to help treat a disease. NKGen focuses on other means to enhance the 40 plus receptors of natural killer cells, making them more receptive and sensitive to picking out cancer cells.
Paul Y. Song, MD is currently CEO and Vice Chairman of NKGen Biotech. Dr. Song’s last clinical role was Asst. Professor at the Samuel Oschin Cancer Center at Cedars Sinai Medical Center.
Dr. Song served as the very first visiting fellow on healthcare policy in the California Department of Insurance in 2013.He is currently on the advisory board of the Pritzker School of Molecular Engineering at the University of Chicago and a board member of Mercy Corps, The Center for Health and Democracy, and Gideon’s Promise.
Dr. Song graduated with honors from the University of Chicago and received his MD from George Washington University. He completed his residency in radiation oncology at the University of Chicago where he served as Chief Resident and did a brachytherapy fellowship at the Institute Gustave Roussy in Villejuif, France. He was also awarded an ASTRO research fellowship in 1995 for his research in radiation inducible gene therapy.
With Dr. Song’s leadership, NKGen Biotech’s work on natural killer cells represents cutting-edge science leading to key findings and important pieces of the puzzle for treating two of humanity’s most intractable diseases.
- Paul Song LinkedIn
- NKGen Biotech on Twitter - @NKGenBiotech
- NKGen Website: https://nkgenbiotech.com/
- NKGen appoints Paul Song
- Patient Story: https://pix11.com/news/local-news/long-island/promising-new-treatment-for-advanced-alzheimers-patients/
- FDA Clearance: https://nkgenbiotech.com/nkgen-biotech-receives-ind-clearance-from-fda-for-snk02-allogeneic-natural-killer-cell-therapy-for-solid-tumors/Q3 earnings data: https://www.nasdaq.com/press-release/nkgen-biotech-inc.-reports-third-quarter-2023-financial-results-and-business