Excellent article overall, most comprehensive real-world account of living with NF-1 I've seen. Thank you.
By Lindsay Toler
By Danny Wicentowski
By Danny Wicentowski
By Jessica Lussenhop
By Lindsay Toler
By Lindsay Toler
By Danielle Marie Mackey
By Lindsay Toler
Like a lot of nineteen-year-olds, Gina Garbo is uncomfortable lounging on the beach in a bathing suit. The main problem is the long brown spot on her left thigh. There are other spots, too, on her legs and belly, but that's the biggest one. It looks like a really odd birthmark. It's not.
Garbo, who grew up in Chesterfield and is a sophomore at Rockhurst University in Kansas City, doesn't drink much, either, not out of moral scruples or a general worry about the dangers of alcohol, but because of a more particular concern for her liver and kidneys. She had a brain tumor when she was twelve, which necessitated nine months of chemotherapy, and she's not sure about the long-term effects of the drugs. To this day she doesn't like to talk about the tumor, about the year she lost her hair and missed a day or two of school every week because she had to go for treatment at St. Louis Children's Hospital.
Now Garbo looks like an ordinary college student. Her hair grew back, long and black, and as long as she's not poolside it's easy to cover up the discolored patches of skin. She tries to see the benefits of having had a brain tumor: a college scholarship from the Pediatric Brain Tumor Foundation, the friends she made at Camp Rainbow, a cancer camp she considers the most wonderful place on the planet.
"This has made me a better person," she says firmly. "If I'm having a really rough day, I think: 'OK, I've been through chemo. It can't get much worse.'"
Like all of us, Garbo doesn't know what health problems she'll face as she grows older. But the spots on her skin and the tumor and the recent difficulties she's had seeing while driving at night are a road map of sorts. They're effects of neurofibromatosis 1, also known as NF1, a genetic disorder that is, in the words of Garbo's doctor, Washington University neuroscientist David Gutmann, "one of the most common disorders most people have never heard of."
One in three thousand people has NF1. (Not to be confused with NF2, which, despite its name, is a completely different disease.) That means it's more widespread than cystic fibrosis or hereditary muscular dystrophy. It's more unpredictable than both those maladies, by a long shot, and at least as misunderstood.
One of the few certainties of an NF1 diagnosis is that the disease won't kill you. Some people develop the café au lait-colored spots, dismiss them as birthmarks and live out their lives without ever hearing of NF1. Some may have Lisch nodules — tiny bumps on the surface of the eye that have no effect on vision and are easily ignored.
Others, like Garbo, develop optic-nerve tumors, which sometimes spread to the hypothalamus and cause growth problems.
Still others are afflicted with neurofibromas or the larger plexiform neurofibromas, benign tumors that can cause a sharp pain if bumped or, depending upon where they're located, push soft, still-growing bones out of alignment. Some children develop heart murmurs.
Then there are the invisible complications — learning disabilities and behavioral problems, lack of physical coordination and the social issues that come from being a kid who's bad at school and sports.
"There are so many potential things with NF," says Gina's mother, Terri Garbo. "It was hard to know what to tell Gina when she was younger, how much information is enough or too much. She can spend a lot of time worrying about things that can come to pass. It's better to move forward."
When David Gutmann quips that most people have never heard of NF1, he's ignoring the fact that for more than a century, the disorder was known as Elephant Man's disease. Shortly after he was born in Leicester, England, in 1862, Joseph Merrick developed grotesque tumors all over his face and body, thought to have been caused in utero, when his mother was knocked over by a circus elephant. Before he died in 1890 — of asphyxiation from tumors blocking his airway — he made his living as a sideshow attraction.
Though his story became the infamous stuff of legend, fodder for stage and screen, when researchers at the University of Michigan discovered the gene that causes NF1 in the late 1980s, scientists began to reconsider whether Merrick actually had something else. Gutmann, for one, is certain Merrick's affliction was a much rarer disease called Proteus syndrome. But the association stuck. As recently as eleven years ago, when Anna Gavrielson was diagnosed, a doctor told her parents she had Elephant Man's disease.
"It's pretty devastating if you've seen the movie," says the girl's mother, Marie Gavrielson.
"Dr. Gutmann alleviated that," Gavrielson continues. "He said, 'We'll see. We're not sure. It presents differently [in different people].' Anna's a normal child. She just has funky bumps." ("They only hurt when I get hit," Anna, who is now twelve, hastens to add. "I have to be more careful when I'm playing. Like when we do dodgeball, I try to keep my back to the wall.")
Few people understand NF1's complexity better than Gutmann, who was doing his postdoctoral fellowship at Michigan when the gene was isolated. He has been studying the disorder ever since.
Most of his fellow UM researchers were what Gutmann, now 53, calls "gene jockeys": Like early polar explorers, they were eager to make the discovery, plant their flag and move on. Gutmann preferred to stick around and survey the territory. He'd trained as a neurologist and was fascinated by how mutations in genes turn into diseases. If he could figure out how the dysfunctional NF1 gene wreaked its havoc, he reasoned, he might be able to reverse the process. He arrived at Wash. U. in the fall of 1993 and set up a lab and a clinic to see patients — among them Gina Garbo, who was first brought in when she was two months old.
He was, by his own admission, a great success. He published papers, drew patients from across the country and, within nine years, had an endowed chair at the university. It wasn't enough.
Gutmann understood genetics, neurology and immunology, but he didn't know what made brain tumors grow or how bones develop or how to deal with learning and behavioral problems. He could consult or even refer his patients to specialists in these areas, but that did little to improve his understanding of NF1.
"You're not just a gall bladder or lungs," Gutmann says. "You're an entire system. You need to understand what the other person does. Otherwise it's like people bringing in a car with something wrong. I can do the oil filter, and someone else can do the tires, but the problem might be something totally different. There's a lot of information out there, both clinical and research. It's not in one pot anymore."
In a sense, Gutmann realized, he had to be like the NF1 gene: tapping into every system the disease touched. So he began knocking on doors. In a single year, he estimates, he talked to between 60 and 80 people. "It was a long first date," he quips. In the end he found six collaborators who agreed that NF1 would be a good model for their own investigations.
A child with NF1 has a 20 to 30 percent chance of developing brain tumors. That statistic caught the attention of Dr. Josh Rubin, a pediatric oncologist who specializes in brain tumors. As further incentive to collaboration, Gutmann had genetically altered mice to develop the tumors and offered to share.
Wash. U. has long encouraged that kind of pooling of resources between doctors and scientists in different disciplines; it's one of the factors that attracted Gutmann to the university in the first place and why he says he will never leave. But he was also after more than just swapping mice and machines.
"I'd like to create what I call an intellectual biosphere," he explains. "It's commonplace to think about a problem. If two or three people are thinking about the problem, how much better is our understanding if we do it together than if we do it alone?"
The university set aside a large suite on its medical campus, and nine years ago Gutmann expanded his lab and clinic into the NF Center. Though he insists he's merely a member of the team, the space bears the imprint of its creator, right down to the preponderance of University of Michigan banners and decals (Gutmann's undergrad and med school alma mater). More telling is the conference room, which is big enough to hold a dozen collaborators, and the long, narrow hallway in the lab, designed so researchers will bump into one another, literally.
Gutmann has intense dark eyes, magnified by spectacles, and a beard and mustache that are starting to turn gray. He projects an air of authority, confidence and deep seriousness, which he tries to mitigate with a self-deprecating sense of humor.
Patients and parents find his presence reassuring. Pediatrician colleagues say that for a "grownup doctor," he's remarkably comfortable dealing with children, readily bending his tall, lean frame to converse with them at eye level.
Josh Rubin sees something else. "In a different world," he jokes, "David would have been a union organizer. He comes in, persuades you, gets you to believe what he believes and then puts you to work."
The gene that causes NF1 can be inherited, or, as in the cases of both Gina Garbo and Anna Gavrielson, both of whom are the only people in their family with NF1, it can spontaneously mutate.
The gene also behaves differently in everyone who has it, even within a single family.
Take the Crums. For more than 100 years, café au lait spots were so commonplace that the family referred to them as "Crum spots." When Daniel Crum was born with his own Crum spots, his parents Dan and Elizabeth didn't think it was a big deal.
"Then the doctor said, 'I'm sorry, Mrs. Crum, it's a very big deal,'" Elizabeth Crum recalls. "We were like, 'What?' It was devastating for our family."
While Daniel's father has an uneventful array of spots on his chest, Daniel has a brain tumor at the top of his optic nerve, where it intersects with the pituitary gland. He is blind in his left eye, partially blind in his right and is small for his age, easily mistakable for an eighth grader rather than the high school senior he is.
Gutmann believes the NF1 gene's behavior changes depending on other genes it interacts with. It varies, even in families, because many genes are polymorphisms, passed along not as exact copies, but with variations.
It's the same reason there are countless shades of blue eyes.
"My feeling is that what defines the behavior of the tumor that may arise in a person who is very young is different in a person who is nine or ten years old, or if you're a boy or a girl," Gutmann elaborates. "That could be very important. You wonder what the rest of the genes are and what are the effects of the other genes."
Gutmann and Rubin have begun building a genome bank of DNA collected from patients who donate blood samples. So far they have nearly 300 genomes in their collection, but they want many, many more. If they understand how other genes interact with the NF1 gene, they may be able to predict which characteristics of the disease a patient is likely to develop even before the patient begins to exhibit symptoms — the headaches and blurry vision that are harbingers of a brain tumor, for instance — and prevent the tumor from taking root.
But how to prevent a tumor from growing? That question forms the bulk of the research in the NF Center's lab.
The scientists study how changes in the NF1 gene affect how its proteins interact with other proteins, in particular the ones that cause cells to start growing at an abnormally fast rate. They study how noncancerous cells create what Gutmann calls a "permissive environment" that allows cancer cells to proliferate. They study normal nerve cells to figure out what makes them shut down in the presence of an NF1 tumor. (This is the mechanism behind Daniel Crum's blindness.)
And they study stem cells. "All brain cells start as neurological stem cells," Gutmann explains. "We're interested in learning how they work, how they give rise to other cells in the brain, and tumors."
The brain contains 60 percent of the body's cells, many of which have their own special functions. NF1, as Rubin puts it, "takes the brakes off the normal control mechanism." The researchers want to understand how the NF1 gene affects how stem cells grow into their intended functions or turn into tumors instead.
The scientists are also trying to figure out what causes the NF1 gene to exert such a strong influence on thinking and coordination. Many NF1 patients have low muscle tone, and more than half have attention-deficit disorder and some sort of learning disability. Recent studies have shown that mice with both ADD and NF1 have lower levels of the chemical dopamine in their brains. Gutmann suspects it's probably true for people as well, which is why some of his patients with ADD have responded well to Ritalin, which raises dopamine levels.
Above all, though, Gutmann wants to treat his patients as human beings, more than the sum of their genes and cells and proteins.
"It's all about the families," he says. "Not about papers or grants."
In keeping with the collaborative nature of the center, Gutmann requires each patient to contribute to the ongoing research by participating in clinical and drug studies, by donating genetic information or by contributing to the Neurofibromatosis Type 1 Registry, a compilation of medical histories collected from Gutmann's patients and via the Internet. With the aid of a statistician from Wash. U.'s Brown School of Social Work, Team NF has been sorting through the data trying to find common trends and pinpoint the ages at which different symptoms tend to emerge.
"The trick is to identify subgroups and do individualized, personal medicine and find the group most likely to respond," Gutmann says. "That's the reality for NF1. It's a true melding of lab and clinic."
The patients and their families are a valuable source of information about what it's actually like to have NF1 — how it feels when you get hit on a neurofibroma, what it's like to deal with a disfiguring disorder, how to live with the uncertainty of what NF1 might bring next.
Gutmann is not above taking advice from his patients. "One, a girl in college now, e-mailed me recently and said she'd read on the Internet that garlic makes tumors shrink," he says. "I was about to type back, 'I don't think so, but thanks anyway, kiddo.' But she's a smart kid. I decided to pay attention. It turns out that garlic degrades the protein that NF regulates. I love that our families challenge us. They have to be part of the team. They're as important as the researchers and clinicians. They teach us about the condition."
In return, Gutmann teaches the patients about NF1. Gina Garbo, for one, has toured the lab and sat in on meetings and was so inspired that when she got to college, she decided she would, in her words, "pursue NF" by studying psychology and occupational therapy. When she graduates, she hopes to work in Gutmann's clinic.
Gutmann and his medical staff, which includes a nurse practitioner and a team of therapists and administrators, see patients in the clinic at St. Louis Children's Hospital every Thursday. Most patients visit once a year, more often in the event of complications that require monitoring. They come primarily from around the Midwest but from other parts of the nation as well.
Dr. Jonathan Mink, chief of pediatric neurology at the University of Rochester Medical Center, plans to start up his own version of the NF Center later this year and considers Gutmann's clinic a model.
"It's a one-stop shop," Mink says. "The clinic coordinates the care of patients who need to see multiple specialists. David cares for his patients. He manages traffic flow. There's some rallying of the troops to get everyone motivated, but a lot of it is making sure things run smoothly."
In keeping with his mission to treat the whole patient, Gutmann wanted to take the clinic beyond medicine, to help the patients and their families better navigate daily life with NF1. A few years back, the center's physical therapist came up with a plan:
Take the kids rock climbing.
Physical therapist Courtney Dunn joined Team NF nearly three years ago. She's energetic and intensely charismatic. Gutmann describes her as "like a magnet. She'd walk down the street, and people would ask her, 'What can I do?'" Young NF1 patients clamor for the opportunity to sit in her lap and listen intently, even when she tells them stuff like, "Remember, you're brothers: You look out for each other." At the clinic she evaluates patients for developmental delays and works with them on gross motor skills.
Two years ago Dunn came up with the idea of conducting sessions to teach parents how to bring physical therapy into their homes. ("I often hear from parents, 'If my child had a therapist for a parent, we could have therapy all day long, and it would make the kid better,'" she explains.) At the same time, she saw an opportunity to bring the kids together, perhaps encouraging them to broaden their horizons and build confidence.
Thus was born Club NF.
It started small, with a few kids at a public library learning to play chess. Nowadays between 30 and 60 people, including patients, parents, siblings and even a few non-NF1 friends, meet on consecutive weekends six times a year. A grant from the St. Louis Children's Hospital Foundation pays for the outings. While the kids do activities, the parents meet in small groups to talk about their experiences raising NF1 children and discuss practical matters, such as how to integrate therapy into family activities and how to explain the condition and limitations of NF1 to teachers and school administrators.
It's generally agreed among NF Center staff that the session at the Upper Limits rock climbing wall in the summer of 2011 was the most successful the program has had. "The kids were all in harnesses," Dunn recalls, "and they climbed the wall like professionals. It was about ten or fifteen feet. The parents sat on the ground, and some of them cried when their kids reached the top of the wall."
A more recent session at a west-county high school, though it was led by two members of STAGES St. Louis and centered on singing, dancing and theatrical games, wasn't nearly as dramatic.
But as actress Ashleigh Blevins and dancer Stephanie Fox lead the seven young participants through various activities culminating in a pair of song-and-dance routines — "Oh, the Thinks You Can Think!" from the musical Seussical and "Fireball" by Willow Smith — it becomes difficult to think of the morning's activities as physical therapy.
True, the kids tend to have trouble coordinating the singing with the pivot step and jazz hands, but so do the Team NF staffers and high school volunteers. And true, the kids are unruly. They'd rather play games than learn a dance routine, and at the games, they cheat. But there are no signs of tumors or anything else that would indicate that any of the children has a congenital disease, except for a pair of flesh-colored braces ten-year-old Sarah Branson wears on her ankles.
(Several of the families who come to Club NF have more than one kid with the condition, but none surpasses the Bransons, Sarah and her sister Lily, fourteen, and brother Isaac, seven. Their father, Charles Branson, has NF1, as does his mother. Pam Branson says she and Charles were aware they had a 50 percent chance of passing on the gene with each pregnancy. They were, she says, "blessed with all three.")
While the children rehearse, the parents gather in a nearby classroom to discuss how to be better advocates for their kids at school. Alicia Vallorani, the NF Center's clinical research assistant, and Dunn demonstrate different iPad apps, including games to help improve fine motor skills and a utility that converts PDF files into text documents so that kids who have trouble holding a pencil can do homework assignments electronically.
"Families with NF kids are such an open group," Dunn says. "They're searching for input and health. They're interested in things they can put into practice. They want specific tools to make sure the kids succeed. It's an easy group to work with."
When the parents wrap up, they venture into the auditorium to watch the dance routines. "Oh, no!" Sarah Branson groans at the sight of her mom. Isaac covers his eyes as he stumbles through "Oh, the Thinks You Can Think!"
The parents applaud.
Gutmann takes a hands-off approach to Club NF. "Other people come up with these things," he says. "I just say, 'What cool things can we do?' and other people come up with them."
But things like Club NF and the iPad apps fit with his philosophy that the NF Center should treat the whole patient, not just the tumors and neurons.
"If you have an ego, you need to get out of science," he says. "Most of what we do now will, in 50 years, be a footnote. I've moved the field along. None of us are in it to be the face of NF. Fifty years from now, the best I can hope for is that someone will read one of my journal articles and say, 'That was cool — for that time.' I'm OK with that. We've made small, incremental advances."
Gutmann still hopes to be able to raise the disease's public profile.
"In the Jerry Lewis telethon, you have the kid who can't walk," he explains. "It's easy to tug at the heartstrings and get people to write a check. With NF you have relatively normal kids with issues, or something really difficult to look at, like the adult with thousands of neurofibromas. Then you cross the line of empathy. It's a tough line to walk. You don't want to scare people off. NF1 patients are normal people with unpredictable lives."
Gutmann hasn't had much trouble, though, winning grants to fund his work in the lab. His latest project, funded by the James S. McDonnell Foundation, is to map the ecosystem of a mouse brain tumor. Like a diagram of an ecological ecosystem, the map will account for every single cell, protein, system and neurological pathway and how all the pieces work together.
"We want to take the system apart and see what makes it possible for it to function," he says. "No one has ever tried anything like this before."
Like Gutmann's previous collaborations, the project will involve researchers from disciplines throughout the university and beyond, from neurologists to mathematicians to radiologists to technicians who've developed microscopes to examine the individual cells. "It'll take us a year of quality first dates before we're all able to talk the same language," he says.
He's not sure if this map will be the one true guide to understanding the more puzzling aspects of NF1 that still elude him. In the meantime, he'll still be seeing patients and continuing his lab and clinical research.
"I'm fortunate to be able to do what I'm doing," he says. "People gripe about the changes in medical practice, the NIH's shrinking budget. I'm lucky. I have an opportunity every day to take care of individuals whose conditions I understand well. Then I get to unravel more of the mystery in the lab. I have a fantastic group of people in the NF Center to talk with. I can see what the future might look like. It's exciting to be part of that, exhilarating and fun."
Excellent article overall, most comprehensive real-world account of living with NF-1 I've seen. Thank you.
I found this article and research to be positive and hopeful. Unfortunately, I am unable to share in this hope as I am presently watching a family member suffer with this condition without proper medical care. He underwent surgery while in grade school to remove tumors, and was given the diagnosis at that point. Unfortunately, during that time, there was no discussion of ongoing treatment, neurological conditions, possible limitations, etc. He currently has tumors on his back, lower adomen, and near his groin area which covers a lot of his body surface area considering he is over 30, but has the small frame of a 14-16 year old adolescent. Without access to care, he self medicates, and his family has been unable to convince him to seek treatment due to financial limitations. As I continue to search the WWW for methods to assist him, I would like to encourage all the parents with a child with this diagnosis to take advantage of all of the options that you receive regarding education, treatment, and DOCUMENTATION. Unless this common disorder that no one has heard of is studied and documented more consistently, the symptoms (especially neurological) and affects on daily living will be considered unrelated as your 'seemingly normal' children are expected to become productive adults in society.
Anon is correct and hopefully the author will update what is overall a very good article. One of the challenges of NF1 is it's variability. Thankfully NF1 does not have the early death rates of some other genetic disorders (Huntington's disease, cystic fibrosis etc.) but you can die from it. Most cases of early mortality occur when the plexiform tumors transform into Malignant Peripheral Nerve Sheath Tumors (MPSNT). Fortunately this occurs in only 5-10% of the cases, but it is meaningful, and there are other complications of NF1 that can impact life expectancy. John Risner
"One of the few certainties of an NF1 diagnosis is that the disease won't kill you." A disappointing and inaccurate description of NF1. MPNST, tumor infringement on vital organs, airway obstruction, blood vessel anomalies leading to aneurysm/bleeding/stroke or other complications, and complications from severe hydrocephalus are just a few of the reasons people with NF1 lose their battle. Common? no.... But these occur in NF patients and it is dismissive to make the claim listed above. I am saddened that this sentence was included in an otherwise good article.