One Gene Mutation Links Three Mysterious, Debilitating Diseases


On a good day, my shoulders, knees, and hips will dislocate two to five times apiece. The slightest bump into a table or door will bloom new bruises on my arms and legs or tear a gash in the thin skin on my hands. My blood pressure will plummet each time I stand, making me feel woozy, nauseated, and weak. I’ll have trouble focusing and remembering words. I’ll run my errands from underneath an umbrella to prevent an allergic reaction to the Sun.

I have Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS)—a trifecta of weird diseases. POTS, EDS, and MCAS are so obscure that many doctors have never even heard of them. But a 2016 study published in Nature Genetics might help change that: Researchers have found a genetic mutation that links all three conditions.

There are at least six types of EDS, all caused by defective connective tissue. I’ve got the most common form, Hypermobility Type (EDS-HT), also known as EDS-III. EDS-HT is considered the most “benign” form—that is, it’s generally not fatal—but the chronic pain, injuries, and other symptoms it causes can easily take over a person’s life.

POTS is a form of dysautonomia, or dysfunction of the autonomic nervous system (ANS). The ANS manages all the things your body does without thinking, from breathing and pumping blood to digesting food. My POTS is pretty mild; at the moment, the hardest parts are the fatigue and the cognitive issues caused by decreased blood flow to my brain. Other people are not so lucky and may need feeding tubes or constant bed rest.

MCAS, also called Mast Cell Activation Disease, is the newest and potentially the trickiest of the three. Mast cells are generally heroes in the body, helping keep the immune system alert and responsive. But some people have paranoid mast cells that can perceive just about anything (foods, medications, temperatures, deep breathing) as a threat. And when they go off, there’s no telling what will happen; researchers have implicated mast cell activation issues in dozens of symptoms and conditions, from anaphylactic shock to irritable bowel syndrome as well as dysautonomia and connective tissue problems.

People who have EDS-HT often also have POTS or MCAS or both, yet the relationships between the three remain murky. Some scientists think EDS causes POTS. Others think MCAS causes POTS and EDS. But we don’t really know, because there’s been barely any research on any of them. It’s hard to study conditions that look different in every patient (I've never met anyone else with one of these conditions who has a sunlight allergy) and have few, if any, quantifiable symptoms. Another reason for the lack of scientific interest? All three conditions are far more common in women, a trait long associated with meager research funding and minimal medical concern.

Consequently, there are no FDA-approved tests for these diseases, and there are certainly no cures. People with EDS-HT wear joint braces to reduce dislocations and are taught to manage their pain. People with POTS are prescribed beta blockers, high-sodium diets, and compression gear to keep up their blood pressure. People with MCAS are given antihistamines.

EDS-HT is typically passed from parent to child, and scientists have found genetic markers for other types of EDS, so it’s not unreasonable to think that it could be caused by mutated DNA.

Fortunately, the cost of DNA sequencing has continued to drop, and clusters of researchers around the world are beginning to take a look. The latest study, led by Joshua Milner at the National Institute of Allergy and Infectious Diseases, involved 96 people with EDS-HT and mast cell issues. POTS symptoms were common, especially gut problems like Irritable Bowel Syndrome.

The study participants had another thing in common: higher-than-normal levels of a protein called tryptase in their blood. Tryptase is part of the immune system’s reaction and has been linked to a handful of core EDS-HT and POTS symptoms, Milner says.

"Tryptase can contribute to pain sensitivity," he told me. "It can contribute to blood vessels doing funny things, and it can contribute to how your connective tissue, your bones and joints, are made."

Most people with mast cell issues actually have normal levels of tryptase, so the group Milner and his colleagues tested represented just a small subset of mast cell patients. But that subset did seem to have a unique genetic signature: an extra copy of a gene called TPSAB1. Under normal circumstances, TPSAB1 makes a form of tryptase called alpha-tryptase. People with a double dose of the gene are getting a double dose of the protein, too.

Armed with this clue, the researchers then went back through thousands of patient records for healthy people. When they looked at the DNA results of people with high tryptase levels, they found that all of them also had the TPSAB1 mutation. The scientists then interviewed a number of these supposedly hearty specimens and found that all of them were living with symptoms that sounded suspiciously similar to those of EDS-HT, POTS, and MCAS. They'd just never been diagnosed. (This is unsurprising—the average time to diagnosis for a person with EDS-HT is 10 years.)

In short, Milner and his team had discovered a genetic biomarker for Ehlers-Danlos Syndrome. Now, EDS-HT is a very variable condition, and the few experts that do exist suspect it's actually a bunch of different diseases called by the same name. Still, this finding represents one possible clinical test for what has been an un-testable illness.

Alpha-tryptase is a funny thing. About 30 percent of people don't make it at all, and they seem just fine without it, which means that a potential treatment pathway for the EDS-HT/MCAS/POTS hat trick could involve simply shutting down the alpha-tryptase factory.

It’s "interesting work," says Lawrence Afrin, a hematologist at the University of Minnesota. He told me the study represents "early progress toward further unraveling these illnesses." And Afrin should know: he's one of the leading MCAS experts in the country.

He agrees that alpha-tryptase could be a promising avenue for treatment. "But if I've learned anything about [MCAS]," he says, "it's that it's incredibly complex. Hopefully, with another 10,000 studies, we'll make 10,000 more bits of progress."

In the meantime, people with EDS, POTS, and MCAS have found other ways to cope. Communities of patients have popped up in cities across the globe and all over Twitter, Tumblr, and elsewhere on the web. These illnesses can be incredibly isolating and lonely—but, as I've learned, none of us are alone.

If you recognize yourself or your symptoms in this story, read up on the basics of EDS, MCAS, and POTS, and brace yourself for an uphill battle.

"Find a local physician who’s willing to learn," Afrin advises.

"And try to be patient," Milner says. "I know it's hard, but stick with it. We're all figuring this out together."

Know of something you think we should cover? Email us at

This Just In
Yes, Parents Do Play Favorites—And Often Love Their Youngest Kid Best

If you have brothers or sisters, there was probably a point in your youth when you spent significant time bickering over—or at least privately obsessing over—whom Mom and Dad loved best. Was it the oldest sibling? The baby of the family? The seemingly forgotten middle kid?

As much as we'd like to believe that parents love all of their children equally, some parents do, apparently, love their youngest best, according to The Independent. A recent survey from the parenting website Mumsnet and its sister site, the grandparent-focused Gransnet, found that favoritism affects both parents and grandparents.

Out of 1185 parents and 1111 grandparents, 23 percent of parents and 42 percent of grandparents admitted to have a favorite out of their children or grandchildren. For parents, that tended to be the youngest—56 percent of those parents with a favorite said they preferred the baby of the family. Almost 40 percent of the grandparents with a favorite, meanwhile, preferred the oldest. Despite these numbers, half of the respondents thought having a favorite among their children and grandchildren is "awful," and the majority think it's damaging for that child's siblings.

Now, this isn't to say that youngest children experience blatant favoritism across all families. This wasn't a scientific study, and with only a few thousand users, the number of people with favorites is actually not as high as it might seem—23 percent is only around 272 parents, for instance. But other studies with a bit more scientific rigor have indicated that parents do usually have favorites among their children. In one study, 70 percent of fathers and 74 percent of mothers admitted to showing favoritism in their parenting. "Parents need to know that favoritism is normal," psychologist Ellen Weber Libby, who specializes in family dynamics, told The Wall Street Journal in 2017.

But youngest kids don't always feel the most loved. A 2005 study found that oldest children tended to feel like the preferred ones, and youngest children felt like their parents were biased toward their older siblings. Another study released in 2017 found that when youngest kids did feel like there was preferential treatment in their family, their relationships with their parents were more greatly affected than their older siblings, either for better (if they sensed they were the favorite) or for worse (if they sensed their siblings were). Feeling like the favorite or the lesser sibling didn't tend to affect older siblings' relationships with their parents.

However, the author of that study, Brigham Young University professor Alex Jensen, noted in a press release at the time that whether or not favoritism affects children tends to depend on how that favoritism is shown. "When parents are more loving and they're more supportive and consistent with all of the kids, the favoritism tends to not matter as much," he said, advising that “you need to treat them fairly, but not equally.” Sadly for those who don't feel like the golden child, a different study in 2016 suggests that there's not much you can do about it—mothers, at least, rarely change which child they favor most, even over the course of a lifetime.

[h/t The Independent]

15 Scientific Reasons Spring Is the Most Delightful Season

Summer, winter, and fall may have their fans, but spring is clearly the most lovable of the four seasons. Not convinced? Here are 15 scientific reasons why spring is great:


road and field on a sunny day

Spring marks the end of blistering winter and the transitional period to scorching summer. In many places, the season brings mild temperatures in the 60s and 70s. People tend to be most comfortable at temperatures of about 72°F, research shows, so the arrival of spring means you can finally ditch the heavy winter layers and still be comfortable.


sunny sky

Following the spring equinox, days begin lasting longer and nights get shorter. Daylight Saving Time, which moves the clock forward starting in March, gives you even more light hours to get things done. Those extra hours of sun can be a major mood-booster, according to some research. A 2016 study of students in counseling at Brigham Young University found that the longer the sun was up during the day, the less mental distress people experienced.


blue bird on branch

Many animals migrate south during the winter, then head north as temperatures rise. For relatively northern regions, there is no better indicator of spring than birds chirping outside your window. Their northward migration can start as early as mid-February and last into June, meaning that throughout the spring, you can expect to see a major avian influx. In addition to the satisfaction of marking species off your bird-watching checklist, seeing more of our feathered friends can make you happy. In 2017, a UK study found that the more birds people could see in their neighborhoods, the better their mental health.


Baby squirrels

Many animals reproduce in the spring, when temperatures are warmer and food is plentiful. Baby bunnies, ducklings, chipmunks, and other adorable animals abound come spring. Studies have found that seeing cute animals can have positive effects on humans. For instance, one small study in 2012 found that when college students looked at cute images of baby animals, they were better at focusing on a task in the lab. Being able to watch fluffy baby squirrels frolic outside your office window might make spring your most productive season of the year.


flowers hanging outside of a house

In 2015, a pair of public policy researchers discovered a hidden upside to "springing forward" for Daylight Saving Time. It reduced crime. When the sun set later in the evening, the study published in the Review of Economics and Statistics found, robbery rates fell. After Daylight Saving Time started in the spring, there was a 27 percent drop in robberies during that extra hour of evening sunlight, and a 7 percent drop over the course of the whole day.


child with rainbow umbrella jumping in puddle

Warmer temperatures mean you can spend more time outside without freezing your feet off, which is great for mental health. Across the seasons, research has found that taking walks in nature slows your heart rate and makes you more relaxed, but some research indicates that there is something special about spring's effect on your brain. A 2005 study from the University of Michigan linked spending 30 minutes or more outside in warm, sunny spring weather to higher mood and better memory. But the effect reverses when spring ends, since being outside in the warmest days of summer is usually pretty uncomfortable.


woman writing in a park

That same University of Michigan study found that spending time outside in the sunny spring weather isn't just a mood booster, it actually can change the way people think. The researchers found that being outdoors broadened participants' minds, leaving them more open to new information and creative thoughts.


leaves budding in spring

Spring brings green growth back to plants and trees. Depending on where you live, trees may begin sporting new leaves as early as mid-March. That successful spring leaf growth ensures a cool canopy to relax under during the hot summer—a hugely important factor in keeping cities comfortable. According to researchers, vegetation plays a big role in mitigating the urban heat island effect. When trees release water back into the air through evapotranspiration, it can cool down the areas around them by up to 9°F, according to the EPA.


tulip bulbs

It's amazing what a little sun can do for plants and grass. Through photosynthesis, plants convert sunlight, carbon dioxide, and water into food, releasing oxygen in the process. That means as plants start to grow in the spring, they pull carbon out of the atmosphere, providing an important environmental service. Plants take in roughly 25 percent of the carbon emissions humans produce, absorbing more than 100 gigatons of carbon through photosynthesis each growing season. Because of this, the amount of carbon dioxide in the atmosphere drops each spring and summer. (Unfortunately, it rises in the winter, when most plants aren't growing.)


wooden box full of fresh produce

Many vegetables and some fruits are harvested in the spring. 'Tis the season to get your local asparagus, greens, peas, rhubarb, and other fresh produce. Getting more fruits and vegetables into your diet isn't just good for the body; it's good for the soul. A 2016 study of more than 12,000 Australians found that when people increased the amount of fruits and vegetables in their diet, they felt happier and had higher rates of life satisfaction. If they increased their intake by eight portions a day (a tall order, we know) the psychological gains were equivalent to the change in well-being people experience when they go from being unemployed to having a job, the researchers found.


Flowers in a vase

After months spent conserving energy, flowers bloom in the spring, once they sense that the days have grown longer and the weather has turned warmer. That's good for humans, because several studies have shown that looking at flowers can make you happy. A 2008 study of hospital patients found that having flowers in the room made people feel more positive and reduced their pain and anxiety [PDF]. Another study from Rutgers University found that when participants were presented with a bouquet of flowers, it resulted in what scientists call a "true smile" a full 100 percent of the time. Seeing flowers had both "immediate and long-term effects" that resulted in elevated moods for days afterward, according to the researchers [PDF].


woman tying shoes in flower field

While it's important to keep moving no matter what the weather, research shows that working out can be more beneficial if you do it outside. A 2011 study found that, compared with an indoor workout, exercising outdoors in nature increased energy levels, made people feel revitalized, and decreased tension, among other positive effects. People who worked out in the fresh air also tended to say they enjoyed the experience more and would be likely to repeat it, suggesting that using nature as your gym might help you stick with your exercise regimen. While those benefits probably extend to winter, too, it's a whole lot easier to stomach the idea of a run once the weather warms up.


dew on grass and a daisy

Flu season in the U.S. typically lasts through the fall and winter, usually peaking between December and February and tapering off during the spring. The seasonal change is in part because of dry air. Cold temperatures mean a drop in humidity, and indoor heating only makes the air drier. This lack of moisture in the air can dry out your skin and the nasal cavities, leading to nose bleeds, irritated sinuses, and a greater risk of getting sick. Since the mucus in your nose is designed to trap viruses, when it dries up, you're more likely to catch something nasty, like the flu. As the weather warms up and becomes more humid throughout the spring, that mucus comes back. As the season wears on, not only can you lay off the body lotion, but you can probably put away the tissues—if you don't have spring allergies, that is.


windows open on a red house

Temperate weather makes it easier to get the fresh air you need. Opening your windows and allowing the breeze in serves as an important way to ventilate indoor spaces, according to the EPA. A lack of ventilation can lead to an unhealthy concentration of indoor pollutants from sources like cleaning product fumes, certain furniture and building materials, and stoves (especially gas ones), posing a threat to your health and comfort. Winter brings the highest rates of indoor pollutants like nitrogen oxide, a 2016 study of unventilated stove use in homes found. Spring brings the perfect opportunity to throw open those windows and doors and get the air moving again.


woman enjoying sitting in the sun

Sunlight triggers your body to produce the vitamin D, which keeps your bones strong. At northern latitudes, it's extremely difficult to get enough sun exposure naturally to maintain healthy vitamin D levels during the winter—even if you did want to expose your skin to the elements—but that starts to change during the spring. One Spanish study found that in Valencia (which shares a latitude with Philadelphia, Denver, Baltimore, Kansas City, and several other major U.S. cities), people only need 10 minutes outside with a quarter of their bodies exposed to the spring sunshine to get an adequate daily dose of vitamin D.

A version of this story originally ran in 2014.