At 6:30 in the morning, at the end of an upscale San Ramon cul-de-sac, eight-year-old Lucas Clark is waking up. He lies blearily in bed, covers pulled up to his neck, staring fixedly at his big-screen TV. His twin sister, Courtney, and ten-year-old sister, Sydney, put the finishing touches on their school outfits when they aren’t darting in to peek at Lucas’ cartoons. Their father, Dean, an affable software engineer, shakes his son out of bed, while their mother, Stefanie, assembles breakfasts and lunchboxes and calls for Lucas to come feed the dog.
A loud humming and the tempestuous drumming of feet on stairs announce Lucas’ somewhat grumpy arrival in the kitchen.
Lucas Clark gets a push from his twin, Courtney. Credits: Chris Duffey The Clark family at dinner. Clockwise from far left: Dean, Courtney, Lucas, Stefanie, and Sydney. Credits: Chris Duffey Lucas prefers time alone, absorbed in his favorite cartoons. Credits: Chris Duffey Graham Mueller gets a hug from his mom, Cindy, and chews on a plastic toy designed to help soothe him. Credits: Courtesy of the Mueller family Lucas’ aversion to cameras makes family photos like this one difficult. Credits: Courtesy of the Clark Family
“You didn’t get dressed yet,” his mom chides.
“Go home!” the pajama-clad Lucas says firmly.
“No, we’re going to school today,” Stefanie says.
“Go home!” he repeats.
“No, we have to go to school.”
“I don’t!”
Ignoring him, Stefanie hands him the dog bowl. Lucas, still humming, goes to the fridge for the can of food, gingerly smells it, and makes a horrible face. At this, everyone holds their breath. Lucas is famous for throwing up around dog food. Instead, he calmly digs at it with a fork and says “Yuck.”
Relieved, Stefanie says, “It’s a big deal that he can just say yuck.”
In fact, it’s a big deal that Lucas can say anything. A year ago, he barely spoke. This morning, he’s practically chatty.
“Dog,” he announces, plunking the bowl down.
“Sit!” Stefanie prompts helpfully.
“Sit!” Lucas echoes. The golden retriever obeys.
A few minutes later, Lucas is back in his bed, watching TV and cramming pear slices into his mouth. He still isn’t dressed. “Lucas, where are your clothes?” his mom asks exasperatedly. “Come on, dude.” The clothes she’d set out are mysteriously missing. On a hunch, she checks the laundry hamper. Bingo. She hands them to Lucas, who dresses himself.
Stefanie used to have to wrestle Lucas into his clothes. The sensation of fabric on skin was as repellent to the boy as the smell of dog chow. Grooming was also an uphill battle. “He used to really scream when I would touch his hair,” Stefanie says, spraying water on her son’s scalp and combing his hair. Lucas wriggles and flinches but stays put. With Sydney’s help, his mom corrals him in the bathroom, where she gently holds his mouth open with one hand and brushes his teeth with the other as he continues to struggle. Stefanie counts to ten steadily as she cleans each row of teeth, so he’ll know how long he has left to endure. When she’s mostly finished, Lucas prepares to zoom away.
“Tongue!” she orders, calling him back. “I’m not done.”
It’s hardly your ordinary morning routine, but to the Clarks, Lucas’ voluntary talking, his weakening aversions, and his interest in chores are evidence that he is finally emerging from the isolation of his first eight years. Even the missing clothes could be a sign that Lucas is trying to help out, Stefanie thinks. “He puts dirty clothes back in the closet, and puts any clothes he sees out in the dirty clothes,” she muses. “He’s almost becoming a neat freak.”
For example, just days before, his dad had put some outgoing mail in the box, then saw Lucas bring it back in. Dean had explained to Lucas that this particular mail was supposed to go away. But out of his dad’s sight, Lucas had then thrown the mail in the trash. Was he just trying to help make the mail “go away”? Dean can’t really tell; it’s just one of the many mysteries the Clarks confront every day. He shrugs good-naturedly. “Welcome to Fragile X and autism,” he says. Many people have heard of autism, the brain disorder that impairs social interaction and communication skills. Fragile X syndrome is much less known to the public, despite being the most common inherited cause of mental impairment. The genetic mutation that causes Fragile X is closely linked with many other conditions, including mental retardation, attention deficit disorder, anxiety, and depression, but the most striking overlap is with autism. The conditions share many symptoms, including extreme difficulties with communicating and socializing; repetitive, self-stimulating behavior like Lucas’ loud humming; and the hypersensitivity that makes strong smells or even wearing clothing torturous. Like Lucas, about one third of kids with Fragile X are fully autistic. Another 20 percent fall somewhere on the autism spectrum.
The reverse situation is more complex. Although autism is highly hereditary, 75 percent of cases have no known cause — several genes and perhaps an environmental trigger may be at fault. The remaining cases can be chalked up to a number of single-gene defects, the most common of which is Fragile X, which is responsible for up to 6 percent of all 1 million to 1.5 million autism cases in the United States. That may not sound like much, but to scientists, Fragile X is highly significant. They know the gene’s location, what goes wrong with it, and how it can cause many of the symptoms shared by Fragile X and autistic kids. Armed with new insights into the chemical mayhem caused by the faulty Fragile X gene, researchers are working toward the first wave of drugs that can do more than just treat the superficial symptoms of both disorders. Kids who have both disorders, like Lucas, will be their Rosetta Stone.
Lucas, of course, would prefer to be left alone. Like most kids with autism and Fragile X, he’s most comfortable in his private world of cartoons and computer games. He takes in far more information than he gives out.
It was this distant quality that first concerned his parents. As a baby, Lucas smiled at people. He crawled on time. It seemed he would walk before his twin. But by twelve months, Courtney was clearly outpacing him. Long after she could sleep through the night, Lucas still screamed himself to sleep. He was impossible to calm without the aid of a vibrating chair and a recording of white noise. He’d often flap his hands. And most of all, it was hard to get his attention. “I would have to wave my arms and yell at him just to get him to look,” Stefanie recalls.
At first, the Clarks thought his hearing was impaired, but a test came back normal. Finally, after a round of doctors’ visits, someone at Children’s Hospital Oakland ordered the Fragile X blood test. When Lucas was twenty months old, it came back positive. “The day after, I was driving across the San Mateo Bridge and just thinking about having a kid, how you kind of have a map of your life — you know this is the way it looks,” Dean recalls. “And it’s as if somebody just kind of shredded that, and you don’t know where you’re going anymore. You have to go back to reevaluate what life is going to be like with this special little boy.”
Although the Clarks had suspected autism, they knew nothing of Fragile X. “At least with autism, sometimes you can really get your kids to grow out of things,” Stefanie says. “Some kids with autism really do well. But since it was genetic, I realized that it was never going to go away. That was kind of devastating.”
After all, Lucas didn’t look developmentally disabled. Many Fragile X kids have distinct features — a long face and prominent forehead, big ears, and weak muscle tone that makes them slouchy. Lucas could be a clothing-catalogue model, with his snub nose and faint smattering of freckles. What makes his face different is the way his expression rarely mirrors that of other people. Facial mimicry is such a fundamental part of human interaction that it’s profoundly disconcerting when someone won’t play along, when their eyes barely register your presence.
Not that you see his eyes that often. Lucas’ aversion to strong or unexpected stimuli — noise, strange places, new foods, crowds, anything that sticks to his skin — also makes eye contact unbearable. He’ll twist his face away from a lingering look, run from cameras, and turn off tape recorders. There’s hardly a Clark family photograph without Lucas crying and one of his sisters sobbing along sympathetically.
Most people with Fragile X are cognitively delayed, and some are mentally retarded, with IQs under 70. At first, Lucas was placed in special education classes due to his difficult behavior. He would throw massive tantrums, try to escape, eat sand. At one point, the Clarks let his preschool teacher keep him strapped in his car seat.
Perhaps most worrisome, Lucas barely spoke, and his family feared he never would. He learned some sign language and has an electronic talking device, but has to be prompted to use either one. Mainly he hums, in tones ranging from a contented murmur to the roar of an aggrieved Wookiee. “Humming can serve more than one function,” Stefanie says. “It’s either to calm and soothe, or it’s self-stimulatory,” the way some people would tap a foot or bite a pencil. It may also help him block out unexpected environmental noise. But the humming annoyed and even scared his classmates. One year, it so irritated an older disabled kid that he grabbed Lucas hard, leaving bruises.
That did it for the Clarks. They took Lucas to a private specialist, who told them their son was smart enough for a regular classroom. Indeed, Lucas is now doing well in a second-grade class in public school. He can do basic math, write, and read aloud with some prompting. He can draw and paint realistic images and write short stories with the help of his aides. He loves computer games and the Internet. His speech and behavioral therapist Nadia Joseph, who accompanies him to school, took the unusual tack of challenging Lucas’ classmates to help him learn to speak. Now, instead of running away from him, the kids teach him new words.
Nobody can say why Lucas started talking — maybe the therapy, maybe being around kids his age, maybe just maturation — but it started with little notes he would leave around the house. He’d tape them up in his room, or leave them on a table, or write them with sidewalk chalk. First came “french fries,” then “cheeseburger and fries.” Finally it was, “I want cheeseburger and fries from McDonald’s.” To get at his more abstract thoughts, Dean created lists with boxes Lucas could check: I am mad. I am sad. I am bored. Then came a few spoken words: “Go home” popped out a year ago during what was for Lucas an excruciating Disneyland trip.
In the last few months, Lucas has been talking more than ever. His voice is still babyish — high, feathery, and light. He tends to get out only the first syllable, leaving his family to guess his meaning, but still they’re delighted. “We didn’t know he had all this intelligence because he couldn’t express it,” Dean says. “You wouldn’t know when you first meet him — you see this kid that doesn’t look at you, who doesn’t communicate, who seems to be in his world. But it’s all in there.” He pauses. “How do you get it out?”
The Clarks have tried nearly everything — anti-anxiety drugs; the $4,000 talking device; the golden retriever, which actually is a trained service dog. And they started Lucas on intensive behavioral, speech, and occupational therapy within a few months of his diagnosis.
All of this is incredibly expensive. Stefanie estimates that they’ve shelled out about $35,000 just since last July. Seeking partial reimbursement, the family has had several legal skirmishes with Lucas’ school district, which by law must accommodate special-needs students. Now they’re slowly phasing out Joseph, Lucas’ private therapist, for one provided by the district. “It’s expensive stuff, but basically it’s the only thing you can do, so you do it,” Dean says. “Does it work? I don’t know. But you’ve got to try it. … You’ve got to push him, get him out of that autistic box and into society.”
Watching Lucas go to school in the morning is like watching two sets of government operatives exchange top-secret papers. Stefanie bundles the kids into one of the family’s two silver SUVs with CURE FXS and CURE FX license plates and drives to the school, where his transition team of three therapists awaits at the curb. They arrive a half-hour before the bell so they can familiarize Lucas with the day’s schedule. They will assist him in class all day, helping him stay on task, and tracking the “checks” he earns for good behavior. With enough points, today Lucas will earn his favorite thing on earth: a McDonald’s Happy Meal.
Like a swarm of cheerful Secret Service agents, the therapists surround Lucas as he pops out of the car and escort him to the office, calling him back when he runs ahead. The tradeoff is brisk; everyone’s in a hurry. Stefanie has to get the girls to school, then head to the accountant’s office — Lucas-related paperwork is pretty much her full-time job.
Among the experts following Lucas’ progress is Dr. Randi Hagerman, a developmental and behavioral pediatrician at UC Davis’ M.I.N.D. Institute. It would be hard to find a Fragile X kid in the Bay Area who isn’t her patient. A soft-spoken woman with an ash-blond bob, Hagerman did not discover the disorder, which was first described in 1969, but she kick-started American research, starting at the Denver Children’s Hospital in 1980. At the time, diagnosis technology was primitive — doctors would peer through the microscope for X chromosomes that looked broken — but within two years of learning about the disorder she’d made 25 diagnoses. “I’d never had a diagnostic test be positive as frequently as Fragile X,” she recalls. “It was identifying the cause of the mental retardation or autism in many individuals, and yet there was no information out there on it.”
Hagerman’s research team published the first book on Fragile X in 1983, prompting information-hungry parents such as the Clarks to bring their kids to Colorado so she could be their doctor. In 1984, she helped found the National Fragile X Foundation, which is headquartered in Walnut Creek. By 1991, a DNA test became available for the malfunctioning Fragile X gene, and diagnoses boomed.
About one in every 3,600 boys and one in every 4,000 to 6,000 girls has Fragile X syndrome. There are between 75,000 and 100,000 known cases in the US, but Hagerman says the condition is dramatically underdiagnosed, partly because the disorder is anything but uniform. The kids run the gamut from severely retarded to normally intelligent. Those without autism are often sociable and humorous. Girls are generally less severely affected because the disorder is carried on the X chromosome and girls have two — if one is faulty, the other can partially compensate. It’s not unusual for girls with milder Fragile X-related learning disabilities and emotional problems to be overlooked for diagnosis.
One of the more universal symptoms of Fragile X is the brain’s inability to rapidly make and break new neural connections in response to a changing environment. Accordingly, Fragile X kids tend to be slow learners, and skills like walking and talking are often delayed. In general, they are stronger verbally than with math, abstract thinking, and problem solving. Many also experience hyperactivity, anxiety, and depression.
How does the Fragile X gene go awry? The trouble begins when a stretch of DNA turns unstable and starts to skip like a scratched record. As the flawed gene passes from parent to child, the number of skips increases. Someone with 55 to 200 skips may be symptom-free but is likely to have Fragile X kids. Anyone with more than two hundred has the full mutation, and will exhibit symptoms. Because the gene is on the X chromosome, a woman has 50/50 odds of passing it to any of her children. A carrier man will always pass it to his daughters, who inherit his X chromosome, but never to his sons, who only get his Y.
The high degree of Fragile X heritability has profound implications for extended families. Once a child is diagnosed, many other carriers or full mutations already probably exist in the family tree. Since the average age at diagnosis is about two and a half, Hagerman says, many carrier parents have already conceived more children. If the burden of having one Fragile X child is heavy, try having two.
For the past quarter century, doctors have been limited to recommending therapy and treating superficial symptoms. Anti-anxiety or hyperactivity drugs may get kids through the day, but don’t address the core problems. Over the last few years, though, Hagerman’s husband and research partner, UC Davis biological chemist Paul Hagerman, has shed new light on the molecular causes of Fragile X syndrome and its linked condition, autism. “Knowing that a single gene like the Fragile X gene has such a strong association with autism tells us where to look for the things that are going wrong with autism,” he says. “It really gives you a very powerful tool to go after the causes and to think about targeted therapies.”
The normal Fragile X gene, Paul Hagerman explains, produces a protein that acts like an orchestra conductor, regulating other genes, telling them when to produce more proteins and when to stop. But cells with the full mutation shut down the Fragile X gene. The cell then goes haywire, creating chemical deficiencies and surpluses that lead to many of the symptoms of autism and Fragile X.
Understanding which genes misbehave without the conductor is crucial for the development of new medicines, Paul Hagerman says. One of the biggest breakthroughs is the discovery that, without the Fragile X protein, the body makes too much of a chemical that weakens synaptic connections in the brain, essentially making it harder for kids to access the neural network needed to solve problems. “We think that is one of the main causes of the mental retardation,” Randi Hagerman says. Researchers are working on drugs to suppress this pathway — clinical trials for one start this year. Other chemical pathways that misbehave without the Fragile X protein affect anxiety, epilepsy, and synapse structure — all could be promising targets for future therapies.
A more comprehensive, if theoretical, approach would be to switch the gene back on, or at least introduce the Fragile X protein into cells artificially. But the protein needs to be made inside the cells — you couldn’t take it by pill or injection — and it needs to get into brain cells, which are highly protected. Because viruses are one of the few things that can sneak into neurons, researchers have considered using something like an emptied-out HIV virus as a transport vector. However, a virus could recombine with the cell in a dangerous way, or become impossible to control. Accordingly, Paul Hagerman would prefer medicinal therapies to viral ones, but given these difficulties, and the limited funding available, he estimates that it could be three to twenty years before they reach human trials.
Lacking a cure, kids like Lucas rely on therapy. After school, Lucas usually goes to McDonald’s, Target, or PETCO as a reward, and then his therapy team joins him in his bedroom. Behavioral specialist Nadia Joseph takes the lead. She’s a firm, musical-voiced Brazilian woman with wavy black hair, and she sits to Lucas’ right at a small wooden table. To Lucas’ left is his new district-provided aide, Kristen Andersen, a young woman with long blonde hair and several facial piercings. Andersen’s colleague, behavior consultant Becky Mengarelli, sits quietly on the floor.
Lucas reads aloud as Joseph holds his hand, helping him point at each word. After each short book, his therapists ask Lucas about what he read and make him answer questions or draw pictures. Every few minutes, someone asks him if he’s being quiet or staying on task. If yes, he checks a box — another step toward a reward. Lucas normally gets a break every fifteen minutes, and it’s clear how hard it is for him to control his restless body. One leg begins to thump rapidly up and down.
“We should stop here, because it’s gone on too long,” Joseph warns.
“But he’s enjoying it,” Mengarelli notes; Lucas has never read these books before and he seems interested. Yet his hum is turning into a moan. Joseph quietly eases out of her chair, stands behind Lucas, and begins to gently pull his ears, then massage his head and neck.
Andersen helps Lucas draw a picture of a lion. “Don’t they have big teeth?” she prompts. “What about a tail?”
Lucas’ eyes focus on his work, but his body is twisting sideways in his chair; his hand wanders over the tabletop. Joseph increases the gentle pressure to his head, squeezing his scalp as though very gently setting a volleyball. Lucas crawls out of his chair and sits on the floor. Unfazed, Joseph presses on with the lesson. “Now we need to write a sentence. You can write, ‘My lion’s name is …'”
“Lucas!” the boy says. From the waist up, he’s absorbed in the task, but the rest of him is in motion, climbing in and out of the chair, and tipping it back and forth.
“Okay, here, no chair,” Andersen says, taking it away.
“You’re doing good,” Joseph encourages him.
Now leaning onto the table, Lucas’ upper body assumes a rigid posture of little-kid boredom — elbow on table, head propped up on one hand with the palm screwed into his eye socket. But his lower body is flailing wildly. Without stopping the lesson, Joseph grabs one of his waving feet, removes the sock, and gently pounds its sole. She firmly pulls on each of his toes and squeezes his foot. This calms him a bit, but what he really needs is a break. As the therapists gather in the hallway to discuss his progress, Lucas turns on his giant TV and stands with his nose nearly pressed against it.
“Cognitively, Lucas is high,” Mengarelli says. “The challenges for him are less about his abilities and more about how his body controls what goes on. He understands what goes on a lot, but it’s challenging for him to do output.”
Many kids with autism and Fragile X have similar problems — they’re either overstimulated and use avoidance to cope, or they’re understimulated and act out. When Lucas doesn’t get what he needs, Joseph says, he’ll squeeze other people roughly, scream, or throw himself on the ground. The bodywork is meant to stimulate him gently so he can relax and focus. “We’re just trying to center his body,” she says. “His body needs to be fed a special diet of inputs.”
Joseph has worked extensively with Lucas on speech, gently touching his face to show him where to place his tongue and how to move his lips to make different sounds. She’s also learned how to make him understand her. “If I tell him to be quiet, well, for how long?” she asks. “Two days? Five minutes? Everything has to be clear and short and direct. It’s like you’re talking to a foreigner, which is why I feel like him sometimes.”
As tough as the program is for Lucas, he’s lucky to have it. Consider the after-school program for Graham Mueller, an eleven-year-old with the same diagnosis who lives just a few freeway exits away: Nothing.
On a rainy afternoon, his father, Scott, a Baptist pastor, and mother, Cindy, a stay-at-home mom, sit in the living room of their split-level Castro Valley home waiting for the schoolbus when the phone rings. It’s someone from school: Graham just had a bathroom accident, and might be coming home in a rotten mood.
But when the boy bangs through the door minutes later, he happily bounds over to his mother and plants a kiss on her head, then wrestles away from her embrace and flies into the kitchen. His dad chases him up the stairs and into the bathroom with some clean clothes. Graham has a classroom aide, and his family gets some state money for a home aide a few hours a week. Some helpers have been great, some lousy; one did nothing but watch Oprah. The last one quit unexpectedly a few weeks ago. Without her, Graham just does what he likes most after school: endlessly rewinding DVDs to see his favorite cartoon pratfalls over and over.
The last few years have been tough for the Muellers. Like the Clarks, they’ve had to battle their school district, but unlike them, a pastor’s salary doesn’t buy many private services. They’ve mostly relied on public special-ed programs, and while they love Graham’s teacher this year, they say previous teachers undid much of the progress he made as a young child. “We’re either falling backward downhill at great speed, or just holding on,” Cindy says. For example, one of Graham’s teachers would punish him with timeouts in the bathroom. “Up until that point he was potty trained,” she says. “Now he doesn’t want to go to the restroom at school and often has accidents.”
Another teacher, they say, was later discovered to be yelling at students and slapping their hands, and others just bored Graham — even after he’d learned the alphabet or how to draw stick figures, they would drill him on easier tasks and eventually he stopped cooperating. “He doesn’t want to show you the same thing over and over,” Cindy says. “He doesn’t want to point at the letter B every day for years on end.” They once tried a private program for autistic kids, but Fragile X kids are great mimics, and being around crying and screaming students only worsened Graham’s behavior.
Graham has the stereotypical elongated face Fragile X, broad forehead, and wide-set eyes, as well as poor muscle tone that makes his movements shambly. When he’s upset he can be violent, throwing fall-down tantrums, kicking, or hitting people. In the third grade, he was suspended for kicking a teacher. He flaps his hands and bites them when he’s stressed; during the first months of school he’ll chew them until they’re leathery with calluses. He’s been slow to learn basic self-care: Graham still needs help in the bath, and dresses himself so slowly his parents often just do it for him.
The boy doesn’t speak, although he constantly shrieks, probably for the same reasons that Lucas hums. He communicates mainly by pointing, or using picture charts to indicate what he wants. Like Lucas, he’s hypersensitive — he can’t wear a Band-Aid for more than a few seconds, and an unexpected U-turn makes him cry. He also hates toothbrushing and binding clothes, which explains his nudist streak. After a few minutes upstairs watching DVDs, Graham comes downstairs for a glass of water wearing just a pair of basketball shorts. His mom is visibly relieved that he’s clothed. But a while later, he’s spotted going back up the staircase al fresco, and his dad has to corner him with some underwear.
The now-undied Graham plops down in front of the TV, puts in a DVD, and cues to his favorite scene, in which SpongeBob SquarePants shovels an enormous ice cream sundae into his mouth at high speed. Graham yells delightedly and mimics shoveling ice cream along with the DVD. He cues up the ten-second clip again. Shovel, rewind. Shovel, rewind. Shovel, rewind. Siblings Ben and Bethany, ages fourteen and sixteen, wander into the kitchen and good-naturedly play along with their brother for a bit, although, truth be told, the yelling and rewinding have become pretty nerve-shredding. It starts every day at 6 a.m.
This isn’t the family life Cindy envisioned. “We have no routine whatsoever,” she sighs. “A lot of times dinnertime rolls around and I’m just like, ‘We’ll just have bowls of cereal and sandwiches.’ A lot of times the house is messy. I’m not the mom I wanted to be or started out to be.”
In fact, the Muellers had planned a life elsewhere — just before Graham was conceived, they were missionaries in Africa, where they’d expected to stay for life. But they fled, leaving everything behind, when civil war broke out in Rwanda. “When we saw the positive pregnancy test, we knew we were not coming back to Africa,” Cindy says. Instead, Scott worked odd jobs planting trees and cleaning toilets, filling in as interim pastor here and there until he was offered his own ministry at East Hills Community Church in Oakland.
Graham was diagnosed with Fragile X when his doctor was concerned that by his first birthday he still wasn’t making typical pretalking sounds and could barely scoot around on the floor. He was diagnosed with autism at age four. Scott’s job is flexible enough that both parents sometimes can be home, but they wonder how they’ll manage when Graham is older. “Sometimes it feels like, okay, can we make it to the end of today?” Scott says. “It’s almost at times too painful to look too far down the road. You think holy cow, puberty is around the corner! It’s heartbreaking whenever we’ve thought about, gosh, is he going to live here? Or, what if we get to a place where we can’t deal with him?”
It’s usually other people who can’t deal with him. Cindy recalls an incident at the park when Scott was pushing Graham on a swing. She begins, “The lady next to him said …
“Something like, ‘Didn’t they have a test to see if he had this before he was born?'” Scott interjects. “In other words, why didn’t you abort this kid?”
“Can you imagine?” Cindy asks, wide-eyed.
“He pushes us to the edge every single day, but that would never be a consideration,” Scott says. “He is the most troubled blessing that we could ever ask for.”
Many Fragile X parents feel alone with their troubled blessings. For most, the first person they talk to following the diagnosis is Robert Miller, head of the National Fragile X Foundation in Walnut Creek (FragileX.org). Often, he says, parents call the foundation’s 800 number from the car on the way home from the pediatrician’s office. He’ll talk as long as they want, and refer them to services they’ll need.
In the Bay Area, the family’s second call is often to Jane Jones, a ponytailed Union City mom who runs the Northern California Fragile X Association, an affiliated group. Her son, sister, nephew, and cousin all have Fragile X syndrome. She is a carrier, as are another sister, her mother, grandfather, and several cousins. She had her son Alex, now nineteen, when she was just nineteen herself, and a single mom to boot. But Jones came out of the gate raring to educate anyone who would listen — teachers, grad students, juvenile court officials. “I would go anywhere,” she says. “I went to the county fair and set up a table next to the farm animals to hand out pamphlets.”
Miller and Jones give comfort to newly diagnosed families who had never heard of Fragile X, or who are dealing with school districts that haven’t. Kids like Lucas and Graham actually have an advantage schoolwise, since autism is well known and schools usually know what to do. “If you check the autism box, your kid gets services,” Stefanie Clark points out. “Well, there is no box for Fragile X.”
The quality of the services often depends on the individual teachers and principal. “I’ve had that question so many times — ‘Can you tell me what the good school districts are?’ And you can’t!” Jones says. “You feel real bad because education is the number one concern with these families for the most part and it’s the hardest thing to pin down.”
Before joining the foundation, Miller had a career in special education, so he knows what it’s like to be on the other side. In 1975, the federal government passed the Individuals with Disabilities Education Act, which compels public schools to provide a “free and appropriate” education to all. But “appropriate” can be a moving target, and the feds supply only part of the funding that school districts need to comply with the law. “Most people who end up as special educators do it because they really care and really want to make a difference, but they don’t have the funds to provide the optimal services,” Miller says.
Furthermore, the law mandates educational services only up to age 21. What happens when Fragile X kids grow up? Some families have the means and temperament to keep their grown kids at home — Dean Clark imagines that he might buy an RV in his retirement and travel cross-country with Lucas. Jane Jones pays for a private group home, where Alex’ education continues, but that can be like paying college tuition — forever. If you’re limited to what government subsidies will cover, Miller says, “finding a group home that is safe and appropriately staffed is a huge challenge for parents. In some parts of the country it simply can’t be found.”
Greater public awareness, Miller says, would help improve the lot of Fragile X kids and adults. “In 1999, the average age of diagnosis of a child with Fragile X Syndrome was around age eight and now it is around age three,” he says. “There has been a tremendous growth in the awareness, but it’s still far from where it needs to be.”
While Miller’s group works on lobbying and fund-raising, Jones’ organization hosts support groups, conferences, and social events where Fragile X families can meet people who know precisely what they’re going through. Cindy Mueller recalls a workshop on toothbrushing where the moderator asked parents to share their technique. When one dad timidly volunteered, “Well, first I get him in a headlock …” the room roared with relieved laughter.
Fragile X families simply learn to roll with the absurdities. Sydney Clark will sit stoically as Lucas chews her clothes. Bethany Mueller placidly helps Graham back into his underwear after he streaks her study group. The Clarks can’t stand McDonald’s, and the Muellers are sick to death of SpongeBob SquarePants, but what can they do? Shopping trips are kept short to avoid temper tantrums. Spontaneous cuddling? Not so much. Lucas has to be prompted to hug, and even then he’ll just sort of lean his body against the other person’s. Graham smooches his mom when he gets off the bus, but it’s the same kiss at the same time every day. The Mueller teens have practically become field anthropologists, cataloguing Graham’s quirks: He only likes yellow foods, always uses the right-hand swing, watches TV from weird angles — like reflected in a mirror, or upside down between his legs. Trips out will always be interrupted. “The last time I took him to the movies, we sat in nine different seats,” Scott Mueller recalls.
Fragile X parents have no choice but to laugh. Either that, or give into grief and the guilt — over whether to risk having more kids, over the other siblings who feel ignored, over having a hereditary disease in the family. “Even though realistically you know it wasn’t anything you did — you didn’t OD on drugs, you didn’t eat too much tuna or something — it’s still a personal thing,” Jones says. “I remember having to deal with that, and thinking, gosh, this is something that I passed on to my son.”
Researcher Randi Hagerman stresses the importance of early testing: for newborns, prospective parents, and anyone with a family history of autism, mental retardation, learning disabilities, or mood disorders. But you’ll probably have to ask for it, since some pediatricians are reluctant to test girls or kids who don’t have the distinctive Fragile X look, and because many obstetricians are unfamiliar with the disorder. Even parents of autistic kids are sometimes loath to get tested. “There’s a resistance there because they feel like their child with autism could maybe be cured with just a dietary intervention or something else,” Hagerman says. “When it’s locked into the genes I think it’s scary to them.”
The sun is finally setting on Lucas Clark’s street. On the way home from school, the family stopped at Target where Lucas glommed onto a twelve-pack of Dial, carrying it and gently smelling and touching it like a pet. As his sisters do homework at the kitchen table, Lucas disappears for one of his habitually long baths, during which he’ll use an entire bar of the soap, rubbing it between his hands until it breaks. Stefanie runs out for a haircut, Dean makes dinner, and afterward a very clean Lucas holes up in his room with some computer games.
Around nine o’clock, the pajama-wearing family gathers in the master bathroom for the day’s final task: more toothbrushing. Lucas has helpfully laid out toothbrushes and toothpaste for everyone, and the girls get to brushing. But when it’s his turn, Lucas sprints down the hall. Dean eventually manages to back him into the towel rack and over the sound of scuffling says something like “One, two, three, four, OPEN!, five, six, STOP!, seven, eight, COME HERE PLEASE!” Finally, once he’s been brushed, Lucas’ exhausted parents tuck him into bed and wish him good night.
Tomorrow, and every day until there is a cure, they will get up and do it all over again.
NOT JUST FOR KIDS ANYMORE
People with the Fragile X “pre-mutation” may experience symptoms later in life.
By Kara Platoni
For years, Fragile X syndrome was considered a childhood disability. No one looked for symptoms in adults. But those genes came from someone, and in recent years, husband-and-wife research physicians Randi and Paul Hagerman began noticing some unusual problems in parents and grandparents with the “pre-mutation” – a Fragile X gene damaged insufficiently to cause the full-blown syndrome.
It started with the grandfathers: As seniors, many experience clumsiness, tremors, and memory problems that in some cases descend into dementia. For years, this was misdiagnosed as Alzheimer’s, Parkinson’s, or normal aging. But now there’s proof it’s related to the misbehaving Fragile X gene. In kids with the syndrome, the gene is turned off and doesn’t make a protein crucial for brain development. In the granddads, it’s nearly the opposite problem – the gene makes too many copies of itself, creating a neurotoxic buildup that kills cells and may cause brain shrinkage. The result is called Fragile X-associated Tremor/Ataxia Syndrome, or FXTAS.
Oddly enough, the Hagermans observed, these men often fit a distinctive personality profile: smart, successful, anxious, somewhat obsessive-compulsive, often highly analytical. Many of these, Randi Hagerman points out, are traits Fragile X shares with autism, and men with the pre-mutation are likely to have autistic grandkids. Could it be that, in mild doses, these genetic tendencies are not disabilities, but gifts? “Having the pre-mutation is not all bad,” Hagerman muses. “If you are smart with good verbal skills and a little anxious and a little obsessive-compulsive, you often get higher educational levels. The men we’ve seen, about 45 percent have a master’s degree or higher.”
But the researchers see a darker set of symptoms in carrier moms. Twenty percent enter menopause before age forty – this is dubbed Fragile X-related Premature Ovarian Failure – and 30 percent also have Fragile X-like symptoms including anxiety, depression, learning difficulties, and even mild retardation.
While 75,000 to 100,000 people in the United States have been diagnosed with Fragile X syndrome, researchers estimate that there are up to 400,000 more adults susceptible to either FXTAS or Fragile X-related ovarian failure. Most are probably undiagnosed, particularly if there hasn’t been a Fragile X kid in the family. In many cases, each generation is affected in a different way by the gene. Lucas Clark, for example, has the full-blown syndrome. His mom, who is a carrier, began experiencing ovarian failure in her mid-thirties. The Clarks worry about Lucas’ carrier grandfather, who fits the FXTAS profile but so far hasn’t experienced symptoms. All of the family’s carriers use drugs to combat anxiety and mood instability, which are also Fragile X symptoms.
That the faulty Fragile X gene causes three different conditions in three different demographic groups poses a problem for advocates: For one, it complicates their research and fund-raising efforts. But it may also help broaden public awareness, and pique research interest from the pharmaceutical industry by providing a bigger market of potential patients. “We’re trying to get away from this idea that Fragile X is this condition that causes long narrow faces and big ears and all that,” says Robert Miller, head of the National Fragile X Foundation. “Women with Fragile X-related premature ovarian failure don’t look any different than the general population, and men who have FXTAS don’t look any different.”
Some parents with Fragile X kids are worried that any focus on adult carriers could divide the already meager research pot. But Paul Hagerman thinks it will actually bolster research, and bring in experts from other fields who see Fragile X as a portal to understanding not just autism, but adult neurodegenerative diseases. Most important, he says, understanding one Fragile X-linked condition could provide insight into the others. For example, the finding that an overactive gene causes FXTAS warns researchers not to try and cure Fragile X syndrome by overstimulating the gene’s activity in children. Why solve one problem today only to create a new one tomorrow?
