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."
"A world where people are slotted according to their inborn ability – well, that is Gattaca. That is eugenics."
This was the assessment of Dr. Catherine Bliss, a sociologist who wrote a new book on social science genetics, when asked by MIT Technology Review about polygenic scores that can predict a person's intelligence or performance in school. Like a credit score, a polygenic score is statistical tool that combines a lot of information about a person's genome into a single number. Fears about using polygenic scores for genetic discrimination are understandable, given this country's ugly history of using the science of heredity to justify atrocities like forcible sterilization. But polygenic scores are not the new eugenics. And, rushing to discuss polygenic scores in dystopian terms only contributes to widespread public misunderstanding about genetics.
Can we start genotyping toddlers to identify the budding geniuses among them? The short answer is no.
Let's begin with some background on how polygenic scores are developed. In a genome wide-association study, researchers conduct millions of statistical tests to identify small differences in people's DNA sequence that are correlated with differences in a target outcome (beyond what can attributed to chance or ancestry differences). Successful studies of this sort require enormous sample sizes, but companies like 23andMe are now contributing genetic data from their consumers to research studies, and national biorepositories like U.K. Biobank have put genetic information from hundreds of thousands of people online. When applied to studying blood lipids or myopia, this kind of study strikes people as a straightforward and uncontroversial scientific tool. But it can also be conducted for cognitive and behavioral outcomes, like how many years of school a person has completed. When researchers have finished a genome-wide association study, they are left with a dataset with millions of rows (one for each genetic variant analyzed) and one column with the correlations between each variant and the outcome being studied.
The trick to polygenic scoring is to use these results and apply them to people who weren't participants in the original study. Measure the genes of a new person, weight each one of her millions of genetic variants by its correlation with educational attainment from a genome-wide association study, and then simply add everything up into a single number. Voila! -- you've created a polygenic score for educational attainment. On its face, the idea of "scoring" a person's genotype does immediately suggest Gattaca-type applications. Can we now start screening embryos for their "inborn ability," as Bliss called it? Can we start genotyping toddlers to identify the budding geniuses among them?
The short answer is no. Here are four reasons why dystopian projections about polygenic scores are out of touch with the current science:
The phrase "DNA tests for IQ" makes for an attention-grabbing headline, but it's scientifically meaningless.
First, a polygenic score currently predicts the life outcomes of an individual child with a great deal of uncertainty. The amount of uncertainty around polygenic predictions will decrease in the future, as genetic discovery samples get bigger and genetic studies include more of the variation in the genome, including rare variants that are particular to a few families. But for now, knowing a child's polygenic score predicts his ultimate educational attainment about as well as knowing his family's income, and slightly worse than knowing how far his mother went in school. These pieces of information are also readily available about children before they are born, but no one is writing breathless think-pieces about the dystopian outcomes that will result from knowing whether a pregnant woman graduated from college.
Second, using polygenic scoring for embryo selection requires parents to create embryos using reproductive technology, rather than conceiving them by having sex. The prediction that many women will endure medically-unnecessary IVF, in order to select the embryo with the highest polygenic score, glosses over the invasiveness, indignity, pain, and heartbreak that these hormonal and surgical procedures can entail.
Third, and counterintuitively, a polygenic score might be using DNA to measure aspects of the child's environment. Remember, a child inherits her DNA from her parents, who typically also shape the environment she grows up in. And, children's environments respond to their unique personalities and temperaments. One Icelandic study found that parents' polygenic scores predicted their children's educational attainment, even if the score was constructed using only the half of the parental genome that the child didn't inherit. For example, imagine mom has genetic variant X that makes her more likely to smoke during her pregnancy. Prenatal exposure to nicotine, in turn, affects the child's neurodevelopment, leading to behavior problems in school. The school responds to his behavioral problems with suspension, causing him to miss out on instructional content. A genome-wide association study will collapse this long and winding causal path into a simple correlation -- "genetic variant X is correlated with academic achievement." But, a child's polygenic score, which includes variant X, will partly reflect his likelihood of being exposed to adverse prenatal and school environments.
Finally, the phrase "DNA tests for IQ" makes for an attention-grabbing headline, but it's scientifically meaningless. As I've written previously, it makes sense to talk about a bacterial test for strep throat, because strep throat is a medical condition defined as having streptococcal bacteria growing in the back of your throat. If your strep test is positive, you have strep throat, no matter how serious your symptoms are. But a polygenic score is not a test "for" IQ, because intelligence is not defined at the level of someone's DNA. It doesn't matter how high your polygenic score is, if you can't reason abstractly or learn from experience. Equating your intelligence, a cognitive capacity that is tested behaviorally, with your polygenic score, a number that is a weighted sum of genetic variants discovered to be statistically associated with educational attainment in a hypothesis-free data mining exercise, is misleading about what intelligence is and is not.
The task for many scientists like me, who are interested in understanding why some children do better in school than other children, is to disentangle correlations from causation.
So, if we're not going to build a Gattaca-style genetic hierarchy, what are polygenic scores good for? They are not useless. In fact, they give scientists a valuable new tool for studying how to improve children's lives. The task for many scientists like me, who are interested in understanding why some children do better in school than other children, is to disentangle correlations from causation. The best way to do that is to run an experiment where children are randomized to environments, but often a true experiment is unethical or impractical. You can't randomize children to be born to a teenage mother or to go to school with inexperienced teachers. By statistically controlling for some of the relevant genetic differences between people using a polygenic score, scientists are better able to identify potential environmental causes of differences in children's life outcomes. As we have seen with other methods from genetics, like twin studies, understanding genes illuminates the environment.
Research that examines genetics in relation to social inequality, such as differences in higher education outcomes, will obviously remind people of the horrors of the eugenics movement. Wariness regarding how genetic science will be applied is certainly warranted. But, polygenic scores are not pure measures of "inborn ability," and genome-wide association studies of human intelligence and educational attainment are not inevitably ushering in a new eugenics age.
The rise of remote work is a win-win for people with disabilities and employers
Disability advocates see remote work as a silver lining of the pandemic, a win-win for adults with disabilities and the business world alike.
Any corporate leader would jump at the opportunity to increase their talent pool of potential employees by 15 percent, with all these new hires belonging to an underrepresented minority. That’s especially true given tight labor markets and CEO desires to increase headcount. Yet, too few leaders realize that people with disabilities are the largest minority group in this country, numbering 50 million.
Some executives may dread the extra investments in accommodating people’s disabilities. Yet, providing full-time remote work could suffice, according to a new study by the Economic Innovation Group think tank. The authors found that the employment rate for people with disabilities did not simply reach the pre-pandemic level by mid-2022, but far surpassed it, to the highest rate in over a decade. “Remote work and a strong labor market are helping [individuals with disabilities] find work,” said Adam Ozimek, who led the research and is chief economist at the Economic Innovation Group.
Disability advocates see this development as a silver lining of the pandemic, a win-win for adults with disabilities and the business world alike. For decades before the pandemic, employers had refused requests from workers with disabilities to work remotely, according to Thomas Foley, executive director of the National Disability Institute. During the pandemic, "we all realized that...many of us could work remotely,” Foley says. “[T]hat was disproportionately positive for people with disabilities."
Charles-Edouard Catherine, director of corporate and government relations for the National Organization on Disability, said that remote-work options had been advocated for many years to accommodate disabilities. “It’s a little frustrating that for decades corporate America was saying it’s too complicated, we’ll lose productivity, and now suddenly it’s like, sure, let’s do it.”
The pandemic opened doors for people with disabilities
Early in the pandemic, employment rates dropped for everyone, including people with disabilities, according to Ozimek’s research. However, these rates recovered quickly. In the second quarter of 2022, people with disabilities aged 25 to 54, the prime working age, are 3.5 percent more likely to be employed, compared to before the pandemic.
What about people without disabilites? They are still 1.1 percent less likely to be employed.
These numbers suggest that remote work has enabled a substantial number of people with disabilities to find and retain employment.
“We have a last-in, first-out labor market, and [people with disabilities] are often among the last in and the first out,” Ozimek says. However, this dynamic has changed, with adults with disabilities seeing employment rates recover much faster. Now, the question is whether the new trend will endure, Ozimek adds. “And my conclusion is that not only is it a permanent thing, but it’s going to improve.”
Gene Boes, president and chief executive of the Northwest Center, a Seattle organization that helps people with disabilities become more independent, confirms this finding. “The new world we live in has opened the door a little bit more…because there’s just more demand for labor.”
Long COVID disabilities put a premium on remote work
Remote work can help mitigate the impact of long COVID. The U.S. Centers for Disease Control and Prevention reports that about 19 percent of those who had COVID developed long COVID. Recent Census Bureau data indicates that 16 million working age Americans suffer from it, with economic costs estimated at $3.7 trillion.
Certainly, many of these so-called long-haulers experience relatively mild symptoms - such as loss of smell - which, while troublesome, are not disabling. But other symptoms are serious enough to be disabilities.
According to a recent study from the Federal Reserve Bank of Minneapolis, about a quarter of those with long COVID changed their employment status or working hours. That means long COVID was serious enough to interfere with work for 4 million people. For many, the issue was serious enough to qualify them as disabled.
Indeed, the Federal Reserve Bank of New York found in a just-released study that the number of individuals with disabilities in the U.S. grew by 1.7 million. That growth stemmed mainly from long COVID conditions such as fatigue and brain fog, meaning difficulties with concentration or memory, with 1.3 million people reporting an increase in brain fog since mid-2020.
Many had to drop out of the labor force due to long COVID. Yet, about 900,000 people who are newly disabled have managed to continue working. Without remote work, they might have lost these jobs.
For example, a software engineer at one of my client companies has struggled with brain fog related to long COVID. With remote work, this employee can work during the hours when she feels most mentally alert and focused, even if that means short bursts of productivity throughout the day. With flexible scheduling, she can take rests, meditate, or engage in activities that help her regain focus and energy. Without the need to commute to the office, she can save energy and time and reduce stress, which is crucial when dealing with brain fog.
In fact, the author of the Federal Reserve Bank of New York study notes that long COVID can be considered a disability under the Americans with Disability Act, depending on the specifics of the condition. That means the law can require private employers with fifteen or more staff, as well as government agencies, to make reasonable accommodations for those with long COVID. Richard Deitz, the author of this study, writes in the paper that “telework and flexible scheduling are two accommodations that can be particularly beneficial for workers dealing with fatigue and brain fog.”
The current drive to return to the office, led by many C-suite executives, may need to be reconsidered in light of legal and HR considerations. Arlene S. Kanter, director of the disability law and policy program at the Syracuse University College of Law, said that the question should depend on whether people with disabilities can perform their work well at home, as they did during Covid outbreaks. “[T]hen people with disabilities, as a matter of accommodation, shouldn’t be denied that right,” Kanter said.
Diversity benefits
But companies shouldn’t need to worry about legal regulations. It simply makes dollars and sense to expand their talent pool by 15% of an underrepresented minority. After all, extensive research shows that improving diversity boosts both decision-making and financial performance.
Companies that are offering more flexible work options have already gained significant benefits in terms of diverse hires. In its efforts to adapt to the post-pandemic environment, Meta, the owner of Facebook and Instagram, decided to offer permanent fully remote work options to its entire workforce. And according to Meta chief diversity officer Maxine Williams, the candidates who accepted job offers for remote positions were “substantially more likely” to come from diverse communities: people with disabilities, Black, Hispanic, Alaskan Native, Native American, veterans, and women. The numbers bear out these claims: people with disabilities increased from 4.7 to 6.2 percent of Meta’s employees.
Having consulted for 21 companies to help them transition to hybrid work arrangements, I can confirm that Meta’s numbers aren’t a fluke. The more my clients proved willing to offer remote work, the more staff with disabilities they recruited - and retained. That includes employees with mobility challenges. But it also includes employees with less visible disabilities, such as people with long COVID and immunocompromised people who feel reluctant to put themselves at risk of getting COVID by coming into the office.
Unfortunately, many leaders fail to see the benefits of remote work for underrepresented groups, such as those with disabilities. Some even say the opposite is true, with JP Morgan CEO Jamie Dimon claiming that returning to the office will aid diversity.
What explains this poor executive decision making? Part of the answer comes from a mental blindspot called the in-group bias. Our minds tend to favor and pay attention to the concerns of those in the group of people who seem to look and think like us. Dimon and other executives without disabilities don’t perceive people with disabilities to be part of their in-group. They thus are blind to the concerns of those with disabilities, which leads to misperceptions such as Dimon’s that returning to the office will aid diversity.
In-group bias is one of many dangerous judgment errors known as cognitive biases. They impact decision making in all life areas, ranging from the future of work to relationships.
Another relevant cognitive bias is the empathy gap. This term refers to our difficulty empathizing with those outside of our in-group. The lack of empathy combines with the blindness from the in-group bias, causing executives to ignore the feelings of employees with disabilities and prospective hires.
Omission bias also plays a role. This dangerous judgment error causes us to perceive failure to act as less problematic than acting. Consequently, executives perceive a failure to support the needs of those with disabilities as a minor matter.
Conclusion
The failure to empower people with disabilities through remote work options will prove costly to the bottom lines of companies. Not only are limiting their talent pool by 15 percent, they’re harming their ability to recruit and retain diverse candidates. And as their lawyers and HR departments will tell them, by violating the ADA, they are putting themselves in legal jeopardy.
By contrast, companies like Meta - and my clients - that offer remote work opportunities are seizing a competitive advantage by recruiting these underrepresented candidates. They’re lowering costs of labor while increasing diversity. The future belongs to the savvy companies that offer the flexibility that people with disabilities need.