As much fun as the games are for the athletes participating in them, the Special Olympics are also an uplifting experience for their parents: “It's exciting for us to see Steven do things that we weren't expecting him to be able to do,” says Mandy Striegel, “and to do them so well. Steven has surprised us throughout his entire life. He doesn't give up. He doesn't let the disability get in the way of him going out and doing things.”
WHAT IS TUBEROUS SCLEROSIS COMPLEX?
TSC, which affects 50,000 Americans and one million people worldwide, is “a genetic disease that results in typically benign tumors that can form in almost any organ of the body, but primarily in the brain, kidneys, heart, eyes, and skin,” explains Steven Sparagana, M.D., pediatric neurologist at Texas Scottish Rite Hospital for Children and associate professor of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center and member of the American Academy of Neurology (AAN). Depending on the location and severity of the tumors, people with TSC can be severely mentally and physically disabled, or may seem to be completely unaffected by the disease. Many people aren't even aware they have TSC.
But for those who are adversely affected by the disease, the challenges can be enormous. TSC causes benign brain tumors, called tubers because of their elongated shape. “Those are typically the reason why somebody with TSC might have epilepsy, intellectual disability, autism, and neuropsychiatric problems,” explains Dr. Sparagana. In fact, TSC is a leading genetic cause of epilepsy and autism.
Other TSC brain tumors include subependymal giant cell astrocytomas, which grow within the brain's ventricles—four cavities in which cerebrospinal fluid is created and circulated. Astrocytomas can “obstruct the flow of cerebrospinal fluid, worsen seizures, and cause vision problems and hydrocephalus,” says Dr. Sparagana. (Hydrocephalus is a medical condition in which the brain is not able to properly absorb excess cerebrospinal fluid, leading to an overabundance of fluid in the ventricles, which puts pressures on the tissues of the brain.)
A person with TSC can experience hundreds of seizures a day, often beginning in infancy with infantile spasms that can be very subtle. For example, an infantile spasm can look like a slight head jerk, or as if the baby is trying to do a sit-up. These infantile spasms are very often a key first symptom of the disease.
TSC also causes a host of non-neurologic health problems, including heart tumors called rhabdomyomas, which can often be spotted in a fetus with TSC during a prenatal ultrasound; various skin tumors; lung tumors; and kidney tumors. “It really is overwhelming,” says Kathy Groves. “So many different body systems are involved.” As a result, TSC patients and their families often must work with neurologists, psychiatrists, cardiologists, dermatologists, urologists (doctors specializing in the male and female urinary tract and the male reproductive organs), pulmonologists (doctors specializing in the lungs), and nephrologists (doctors specializing in kidneys) to manage their disease, and “have to make sure that all these doctors are communicating with each other,” Kathy explains.
Often, patients and their families find themselves teaching others about TSC, since it is largely unknown. “You run into doctors who have never heard of this disease,” says Scott Striegel. “You become not just a parent, but an educator.” Kathy Groves knows this frustration all too well: “You can say TSC and that doesn't mean anything.” But, she says, if you tell someone that your child is struggling with “autism, ADHD, bipolar disorder, seizures, mental retardation, kidney tumors”—then the picture becomes quite clear.
Raising awareness is one of the top priorities of the TSC community—and Steven and Ryan are doing just that with their heroic achievements in the Special Olympics.
Oscar-nominated actress Julianne Moore has become an outspoken advocate for people with TSC after the father of a little boy with TSC approached her on the streets of New York City and asked for her help in the fight to raise awareness of the disease. “For something like this that deserves attention, I am happy to use whatever celebrity I have to focus people on tuberous sclerosis,” Moore has said. “The important thing is to get the word out,” says Dr. Sparagana, “and to let people know about the disease.”
A KEY TO OTHER DISEASES?
TSC is a genetic disorder caused by a mutation in one of two genes, TSC1 and TSC2. One copy of the altered gene is sufficient to cause the condition. In one-third of cases, an affected person inherits the altered TSC1 or TSC2 gene from a parent who has the disorder. The other two thirds of TSC cases are spontaneous mutations, meaning neither parent has TSC.
In a healthy person, the TSC1 and TSC2 genes help the body create proteins called hamartin and tuberin, which are integral parts of an important cellular mechanism called the mTOR pathway. When the TSC genes function properly, the mTOR pathway keeps the creation of cell proteins in check, and cells multiply in the correct amounts throughout the body. However, in a person with TSC, a mutation on the TSC1 or TSC2 gene causes problems with hamartin and tuberin and the mTOR pathway; the creation of proteins isn't properly regulated, and cell multiplication runs amok, causing tumors to grow within the body.
Recent years have seen the introduction of a class of drugs called mTOR inhibitors (including everolimus and rapamycin), which “help us overcome deficiencies in the mTOR pathway,” says Dr. Sparagana. These drugs allow the mTOR pathway to be “checked,” he explains, “so you get reduction in protein synthesis, and reduction thereby of tumors.” Currently, the only mTOR inhibitor approved by the U.S. Food and Drug Administration for use in people with TSC is everolimus (brand name Afinitor), which is used to treat subependymal giant cell astrocytomas and also TSC kidney tumors. Several current trials are also examining the use of everolimus for the treatment of autism and epilepsy in people with TSC, and examining rapamycin for the treatment of facial skin tumors in people with TSC.
Some scientists believe the mTOR pathway could be a key to understanding and perhaps treating a host of conditions such as autism, epilepsy, and cancer in people who don't have TSC. “TSC represents a way of understanding many other conditions that affect far greater numbers of people,” according to AAN member neurologist David Franz, M.D., of Cincinnati Children's Hospital. Dr. Sparagana says, “The mTOR pathway is critical to cell function, and function of life, really. A recent article in the Annals of Neurology showed that the mTOR pathway is likely involved in epilepsy of other types not related to TSC. And everolimus already has indications for other tumor types outside of TSC, including renal cell carcinoma (a type of kidney cancer), metastatic breast cancer (a stage of breast cancer in which the disease has spread to another part of the body), and pancreatic neuroendocrine tumors (rare tumors formed in islet cells, which are hormone-producing cells of the pancreas).
According to Elizabeth Henske, M.D., of Brigham and Women's Hospital in Boston, MA, “The same pathway that is abnormal in TSC is abnormal in at least half of cancers.”
The Tuberous Sclerosis Alliance (tsalliance.org), an invaluable resource for patients and families with TSC, so firmly believes in the power of TSC to teach us about other illnesses that they state on their website, “We're Fighting For The Cure That Could Lead To More Cures.” According to the Tuberous Sclerosis Alliance: “Every minute and every dollar spent finding treatments and cures for TSC could [mean] quantum leaps forward in treatments and cures for autism, epilepsy, and cancer.”
Because of all this, says Kathy Groves, “While you may not have TSC touch your life, you may know someone with cancer, or kidney disease, or autism. So the research that furthers knowledge about TSC most certainly impacts hundreds of thousands of individuals across the country and the world who don't have TSC. When you support research into TSC, you're not just helping people with the disease.”
GROWING THROUGH THE GAMES
Steven Striegel and Ryan Groves are already busy with the new basketball season of Special Olympics. “It keeps me physically active,” says Ryan of his participation in the Special Olympics (specialolympics.org), which were founded in the 1960s by Eunice Kennedy Shriver. One of her siblings (in addition to President John F. Kennedy) was Rosemary Kennedy, who was intellectually disabled but who thrived at playing sports with the family, including swimming, sailing, and football. “Through sports, [people with intellectual disabilities] can realize their potential for growth,” Eunice has said. She founded the Special Olympics (originally held in her backyard) to give people with intellectual disabilities “the chance to play, the chance to compete, and the chance to grow.” The Special Olympics are available “at zero cost to participants,” says Kathy Groves. “That's what makes the games so wonderful—regardless of your financial situation, it's an opportunity for the special needs population to have something especially for them, regardless of whether or not you can afford it.”
The Special Olympics are also important in terms of building self-esteem: “If you succeed in one aspect of your life,” says Dr. Sparagana, “you will succeed in other aspects of your life. It helps [the athletes] in terms of their feelings about themselves.” The teams travel together to various tournaments without their parents (volunteers serve as chaperones). This allows them “a chance to be independent, to be responsible for themselves, and do things on their own,” says Kathy Groves. “It's an extraordinary opportunity for them to build their independent living skills.”
Those skills have served Ryan and Steven well. Ryan works as a Courtesy Clerk at a Kroger supermarket (“Kroger is extraordinary in hiring special needs individuals,” says Kathy); and Steven works at a resale center run by a church group. “You have to take things one day at a time when you have a child with special needs,” says Mandy Striegel. “It's hard to plan for the future because you just don't know what's going to happen.” Ryan's parents hope that he can “live as happy, successful, and independent a lifestyle as he can,” says his mother Kathy, “and he is well on his way there.” Ryan lives at home now, and the hope is that one day he can “have his own apartment, where will live, like any 30-something year-old man,” says his mother. In the meantime, “He does his own laundry, he makes his own bed, he can fix you a great spaghetti dinner, and he can make a mean taco casserole from start to finish.” Steven Striegel's father, Scott, says “our hope is that Steven can be productive in society, because I know that makes him feel good—when he goes to his job, and he can do things, and he makes friends.”
In addition to teaching the athletes invaluable skills of independence and self-esteem, the Special Olympics are also an important way for families and people living with TSC and other disabilities to connect, strengthen their communities, and form lasting friendships. “Having a good social network is so important for the mental health of the parents,” says Dr. Sparagana. The Tuberous Sclerosis Alliance, which holds conferences every few years and regularly organizes fundraising events, “gives parents a real support network,” he adds. “It's been instrumental in helping those families.”
Also of great help to the families has been the online revolution: “The social media that is available today allows you to access not just the professionals, but the other parents who already know some of the pitfalls,” says Kathy Groves. “I enjoy that part of it, being able to help those that are following behind Ryan. It's always nice when you can save someone from hitting a wall that you had to hit before you learned how to go around it.” In addition to the comprehensive Tuberous Sclerosis Alliance website, there's tscathletes.tumblr.com and many TSC Facebook pages. Social media, says Kathy Groves, allows the TSC community to “build lifelong friendships” with other parents—“somebody that you can cry to, somebody who truly gets it when your four-year-old finally says ‘Mom.’” Caring for a loved one with TSC can take quite an emotional toll—on the TSC parents, grandparents, and caretakers, says Dr. Sparagana: “I see heroes and saints every day.”
SEARCHING FOR A CURE
While Ryan and Steven's parents hope for their sons' futures, the entire TSC community hopes for a cure: “That's certainly the ideal,” says Dr. Sparagana. “How to get there is a question, because you have a genetic disorder that basically involves a mutation in every cell in the body. The mTOR pathway has been key in understanding the mechanisms by which TSC is occurring,” and thanks to the mTOR inhibitor drugs “we now have a targeted treatment. But even that treatment, as currently presented, is not the be-all-and-end-all,” notes Dr. Sparagana. “There is obviously more to learn here.” Tuberous sclerosis complex, he says, “is appropriately named—it is complex. But fortunately, we are finding out more and more about it.”
Awareness has also been greatly increased over the years: “When I first became involved,” Julianne Moore has said, “I felt like nobody really knew what TSC was. And since then, we've had successful fundraising activities, we've gotten money from the government, and children who had a very poor prognosis are now looking at a much brighter outlook.”
“We decided that we were not going to let this weigh us down,” says Mandy Striegel, “and we were not going to let this weigh Steven down.” Instead, they asked themselves, “let's see what we can do to make things better.” One key way the family is trying to make things better is by Steven's participation in important scientific studies that could lead scientists to answers about TSC—and other diseases that strike millions of people.
“The attitude we have always taken, since Steven was diagnosed with this, was not, ‘Oh my God, why is this happening to me,’” says Scott Striegel, “but more the approach of, Steven has this disability, but can it be used to help other people down the road?” Learning more about this rare disease—and the biological mysteries it encompasses—is so important, says Mandy Striegel, because it just might “open doors that haven't been opened before.”
While science works to find a cure for TSC and the many diseases it can teach us about, Ryan, Steven, and their fellow Special Olympics atheletes keep going for the gold. “Training for the Special Olympics was hard, but it was something I wanted to do,” says Ryan. “I want people with TSC to know that even with the obstacles in your life, you can still do anything you set your mind to.”
FOR MORE INFORMATION
© 2014 American Academy of Neurology
- For more Neurology Now coverage of TSC, go to bit.ly/1gNB5IP
- For coverage of TSC in Neurology Today, go to bit.ly/1gm4Uhd
- For information on seizures in children from Neurology: Clinical Practice, go to bit.ly/1eZgzjl
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