Alyssa Scalia’s infant son, Connor, had gray skin. Her husband, Tom, didn’t see it, but Alyssa didn’t think she could be imagining it. Doctors assured her that she had nothing to worry about; babies just change color a lot.
Similar reassurances followed when Alyssa noticed that Connor failed to hit developmental milestones like walking and talking as quickly as his older brother T.J. had. When Connor finally did start walking, he always walked on tiptoe. This “toe walking” prompted his first misdiagnosis: cerebral palsy.
“That diagnosis was the catalyst for everything else,” says Alyssa. “That’s what started all the testing.” Now that they had confirmed something was wrong, doctors took Alyssa’s complaints more seriously. Tests that were supposed to measure the severity of Connor’s supposed cerebral palsy revealed unexpected abnormalities in his brain, blood, and breathing, which then prompted more testing. Cerebral palsy no longer explained the full constellation of symptoms.
As tests uncovered an ever-growing list of symptoms, Connor’s medical team quickly expanded to include the likes of neurologists, neurosurgeons, hematologists, pulmonologists, and dietitians. Many were from top medical centers in Connecticut, Boston, and New York City, but none could come up with one or even two diagnoses that would explain all the symptoms, nor could they find satisfactory treatments. “We were just shooting darts at a dartboard,” says Alyssa.
Alyssa’s experience is a recurring theme among families touched by rare diseases. Most spend years searching for what is wrong, fighting to get treatment in time if they finally receive a diagnosis. The process is so arduous that patients and experts refer to it as a “diagnostic odyssey.”
Connor’s odyssey included many apparent detours. When he was four years old, an MRI revealed that he had a rare condition known as a Chiari I malformation, in which part of the brain protrudes into the spinal canal. But his malformation didn’t appear serious and had no obvious connection to his full set of symptoms, so doctors decided to leave it untreated for the time being, settling for shooting more darts at the dartboard. “They changed his diet. They smelled his armpits. They just couldn’t figure out what was wrong,” says Alyssa.
When Connor reached third grade, his teacher told his parents that she often let him put aside his work and nap, because he could barely keep his head up. His thick-lashed brown eyes always had dark circles beneath them. Tom took him to a Patriots game, and the young sports fan fell asleep amid the screaming crowd. “It was the loudest game I’ve ever been to, but he just slept like it was no problem,” recalls Tom.
Seeing how Connor’s quality of life kept deteriorating as his sleep issues became more pronounced, the Scalias convinced the medical team to do a sleep study. Connor dragged his feet to the appointment, doubtful that anything useful would come from yet another test. “I was so tired, and I didn’t know what I was doing at all those doctor’s appointments. I questioned it a lot of times. I’d say, ‘It’s fine. I’m just not getting enough sleep,’” Connor remembers, six years later.
Despite his doubts, the sleep study provided crucial information. It turned out that Connor was slowly suffocating his brain as he slept. During the night, he stopped breathing more than 50 times per hour.
The medical team decided they had to operate to correct Connor’s brainstem malformation, which they thought was the cause of the sleeping trouble. But brain surgery only slightly lessened the problem. Connor started sleeping with a breathing machine, and his parents kept watching and waiting for almost two years, hoping for gradual improvement. Nothing changed, and the medical team couldn’t offer further insight.
Finally, when Connor was nearly 12 years old, a friend recommended that the Scalias see Lewis Kass, a pediatric pulmonologist and sleep medicine physician at Norwalk Hospital, in Connecticut. After performing his own sleep study on Connor, Kass called both parents into the office. Alyssa recalls, “He sat us down and said, ‘I haven’t seen it in 20 years, but your son has a very rare genetic condition called CCHS. I’d bet my life on it.’”
Congenital central hypoventilation syndrome (CCHS) is a genetic disorder that affects the autonomic nervous system, which controls the autonomic function of organ systems throughout the body, from breathing and heart rate to the temperature of Connor’s hands and feet. If the autonomic nervous system were functioning normally, it would keep Connor’s entire body running without any conscious thought from him. CCHS, and the resulting failures of the autonomic nervous system, explained nearly all of his symptoms.
The breadth of symptoms was part of what had made Connor’s case so confusing for the doctors he’d been seeing for years. Kass just happened to have spent his medical fellowship working at a CCHS referral center at Yale. Without that experience, he’s not sure he would have recognized Connor’s disease. The same is true for other rare diseases — nonexperts just don’t know what they’re seeing.
As Kass began explaining CCHS and its effects on the autonomic nervous system, a lightbulb went off for Alyssa. She had heard about the autonomic nervous system months before, when New York doctors were trying to figure out why brain surgery hadn’t solved Connor’s sleeping problems. “Does this have something to do with the PHOX2B gene?” she asked. Kass, surprised that she had already heard of the disease-causing gene for CCHS, explained that testing for mutations in PHOX2B would confirm his diagnosis. “They already ordered that test!” exclaimed Alyssa. “It came back negative.”
Perplexed, Kass asked that the test results be forwarded to him. Later that week, he called Alyssa while she was out shopping at Target. The doctor who originally ordered the test — who did not respond to requests for comment for this story — had read the results incorrectly, despite being head of one of the nation’s leading sleep disorder centers.
“To be fair,” says Kass, “the result was buried deep in the report. I didn’t even know what I had when I looked through the paperwork at first. I was actually impressed that she thought to order the test. The report that came back was just a lousy report.”
Kass says Connor’s genetic testing experience is not unique. Debra Weese-Mayer, a leading expert on CCHS at Ann & Robert H. Lurie Children’s Hospital of Chicago who has recommended countless PHOX2B tests, agrees. Both doctors declined to name the commercial genetic testing company involved; however, Weese-Mayer has reached out to initiate a research study to determine how many “missed” cases like Connor’s have occurred. She has learned that commercial labs all too often fail to detect or properly report PHOX2B mutations that she calls “tough to miss.”
“Commercial labs are fine-tuned to do the quick turnaround, high-volume, money-making tests,” explains Casey Rand, senior research project manager under Weese-Mayer. “They do rare diseases sometimes because they have the ability to slash prices and make a small profit. However, they have no real motivation to take time to understand the quirks, like novel mutations, so some families are just ‘sacrificed.’ It’s a problem in every industry — our handbags become cheaper and easier to get, but quality usually suffers,” he says.
Alyssa recognized how fortunate Connor was to get a second opinion that led to an accurate diagnosis, even though it wasn’t an easy diagnosis to receive. “In a moment when most people would feel extreme sadness, I finally felt relief,” she says. “I believed we found what we had been chasing. I had peace for the first time in nearly 12 years.”
Connor didn’t share his mother’s peace at the time. “It was confusing to get a diagnosis, because I didn’t really know what was happening at first,” he says. “Once I went into more detail, it got scary.” Laying out the big picture of all his symptoms for the first time was overwhelming.
To address those scary details, Kass sent the Scalias to Weese-Mayer. Her Center for Autonomic Medicine in Pediatrics in Chicago is one of the world’s only specialty treatment centers for CCHS. Unlike most medical staff, the specialists there weren’t at all surprised by Connor’s symptoms when he arrived there as a 12-year-old.
Alyssa says Chicago was a completely different medical experience. “I felt so safe there. It seemed like for every story I’d tell of Connor’s symptoms, Dr. Weese-Mayer would say, ‘Yes, that’s because of CCHS. It’s an autonomic issue.’”
Even Connor noticed the difference that expertise made. “All their tests were like, wow, this is incredible, how would they know this much about it?” he says.
But those insightful tests, intended to help the doctors develop a precise treatment plan for Connor’s individual set of symptoms, revealed something nobody wanted to see. Weese-Mayer gently pulled Tom and Alyssa aside to tell them there was something abnormal in Connor’s chest X-ray, and they were going to do a CAT scan to look more closely. Weese-Mayer was especially concerned because patients with Connor’s specific type of PHOX2B mutation frequently develop neuroblastoma tumors. “We had read about the tumors but always assumed that wouldn’t be our kid,” says Tom.
The CAT scan confirmed the worst: Behind Connor’s heart lurked a tumor the size of a grapefruit, crushing his aorta. If he had gone undiagnosed any longer, the tumor might have continued growing unseen, increasing pressure on his heart. Even if a doctor had stumbled upon it, removing it without the intervention of autonomic specialists would have been extremely dangerous, because CCHS complicates surgery by making it more difficult to manage breathing and heart rate under anesthesia.
As it was, the unchecked growth had already reached the point where a simple, minimally invasive small-incision removal surgery was impossible. Instead, Connor faced a complex, hours-long open-chest surgery.
A few days before the surgery, Jennifer Reichek, a pediatric oncologist with expertise in neuroblastomas, knelt beside Connor and explained to him that sometimes tumors are bad and sometimes they’re not so bad, but they never belong in his body, so he was going to need surgery to take a tumor out.
“I guess it’s time to get Connor strong,” was Connor’s only reply.
His words helped inspire support from family members, classmates, and friends, as well as the medical team at Lurie. The night before Connor’s surgery, more than a thousand people from the Scalias’ hometown of Monroe, Connecticut, gathered for a vigil on the town green that was livestreamed to Chicago for Connor and his parents. People wore purple T-shirts — Connor’s favorite color — emblazoned with the hashtag #ConnorStrong.
“Connor couldn’t have a better support system,” says Brandon Kuring, a college lacrosse player who mentored Connor through a program called Team Impact. “People gravitate towards him.”
Connor’s support system became increasingly important, as what was supposed to be a weeklong visit to learn more about CCHS turned into an agonizing four-month hospital stay. Although the surgeon successfully removed the tumor, the operation was difficult, and Connor developed serious complications that required surgeons to reopen his incision. As he recovered, support continued in the form of letters, messages from professional athletes Connor admired, and family friends who donated airline miles so all the Scalias could spend Thanksgiving together in Chicago.
Connor finally returned home from the hospital just in time to celebrate Christmas and his 13th birthday. “After four months of not being home, now I never want to leave home,” he jokes.
“Connor just loves to play with the dogs. And sleep with the dogs at night,” says his younger brother Drew. The dogs — fluffy, waist-high Goldendoodles — somehow manage to fit on the bed without disturbing Connor’s breathing machine.
Now tumor-free and armed with knowledge of how to manage CCHS, Connor can dream of the future. He’s “still 50/50” regarding whether he wants to be a veterinarian or a zookeeper. “I have a vision that there’d be like a newly born bear cub that I’d always take care of and train, so when I walk in when it’s older it’ll just give me a huge hug,” he says, smiling shyly.
Connor understands that other patients don’t always have his “happy ending.” Some never get diagnosed; others are diagnosed too late; others have lethal diseases with no real treatment options. But Connor is glad of even the small things he can do to change others’ chances. He has participated in Weese-Mayer’s research studies, and the Scalias also donated his tumor, which he says “feels like the right decision.”
Even as a quiet 15-year-old, he doesn’t mind patiently explaining his disease to people. “I just tell them, ‘My brain doesn’t really tell me to breathe at night, and sometimes during the day,’” Connor says. “Most people seem to get it.”
“You wouldn’t be able to tell that he’s been through a brain surgery and an open-chest surgery. He wears the scar on the back of his head very proudly now,” says his brother T.J.
“I want other people to get educated. We’ve been fortunate in that all our boys are still here,” says Alyssa. “I sometimes think it happened to us because I’m not afraid to talk about it.” The #ConnorStrong Facebook page still has an active following, and Alyssa promotes research and educates others about CCHS whenever she gets the chance, online and off.
Awareness efforts like the Scalias’ do more than help push funding toward rare disease research. Increased awareness can help patients even before medical advances occur. The more doctors know about rare conditions like CCHS, the lower the chances of misdiagnosis — and the better the outcomes for patients like Connor.