In almost all respects, Caleb Metherell is a typical 12-year-old middle school student. He loves sports, Harry Potter, science fiction, and the video game Call of Duty. But unlike his fellow preteens, he has a debilitating involuntary movement disorder called DYT1 dystonia.

DYT1 dystonia typically develops in childhood, although it can begin in early adulthood and, very rarely, later in life. It is caused by a mutation in the DYT1 gene that produces an abnormal protein. The defective protein disrupts communication in neurons that control muscle movement and muscle control.

Slightly more than half of the people who have the physical symptoms of DYT1 dystonia develop involuntary movements, which result in a serious physical disability. The condition does not cause degeneration in the brain and does not affect a person's intelligence or cognitive abilities.

Caleb, for one, is a good student who loves a good pun. But it took some time—and multiple referrals to different specialists—for Caleb's parents, Jim and Cassie Metherell, to find a name for their son's troubling symptoms. This is the story of their journey as a family to find a way forward.

An Early Challenge

Until age five, Caleb was a healthy boy with no signs of the disease. But when he entered preschool, he began to speak intermittently in a gruff voice, not unlike Clint Eastwood's. His parents joked that he was falling in with the wrong preschool crowd and turning into a tough guy.

The "tough guy" moniker became a bit of a family joke because it was so at odds with his personality—he's a sweet, loving boy who tends to joke around and be goofy. They didn't consider it a serious issue at first because the gruffness in his voice occurred only sporadically and didn't cause him any pain or difficulty. Their family doctor agreed that the problem was not serious.

But Caleb's voice slowly changed in other ways. He developed voice breaks, often on the first vowel, but not every time he spoke. These voice breaks were random and unpredictable. His parents suspected he might have a stutter. They consulted speech pathologists and therapists, but speech therapy did not help. Caleb's voice began to break on the first and last words of sentences and then on the hard consonants, and it began to affect the fluency of his speech. Still, at times Caleb could speak without breaks, leading his doctor and speech specialists to consider it a type of stutter.

"Dystonia is often misdiagnosed, especially in children and often early on, in part because it is an uncommon disorder and because the symptoms can be variable," says Caleb's current neurologist, Jonathan W. Mink, MD, PhD, a professor of pediatric neurology and chief of the Division of Child Neurology at the University of Rochester Medical Center in New York. Dr. Mink is also a Fellow of the American Academy of Neurology (FAAN).

"One of the confusing things about dystonia is that it's only present during specific tasks. For example, someone with dystonia may have difficulty walking but no difficulty running, skipping, or dancing. That kind of specificity often leads to confusion among some physicians who may not have experience with dystonia," Dr. Mink explains. "They may think the child who has trouble walking but can hop and run fine could have a psychological problem."

In addition to his speech problems, Caleb developed bizarre movements in conjunction with the speech breaks—his head and trunk would flex forward with each voice break. His doctors couldn't explain it, but Caleb could still speak relatively clearly and he could get around without a problem. Then, suddenly, Caleb developed difficulty standing up. His body would fold into itself, not unlike a pretzel twist.

Caleb insisted he felt no pain. In fact, Dr. Mink, says, "Pain is not common in DYT1 dystonia," though it can occur in other types of dystonias. [See "The Other Dystonias" below.]

Caleb's speech deteriorated gradually over the next two years, but the progression of the involuntary movements in his head and trunk occurred rapidly. "He couldn't walk without being bent all the way over," his dad recalls.

Nearly half of the people diagnosed with DYT1 dystonia develop contractions in the legs; others have abnormal movements in their arms. Very few begin with symptoms in the face or vocal cords, Dr. Mink says. "Caleb was unusual in that [his symptoms] started in his voice, and when a child his age has a voice problem, DYT1 dystonia is probably not very high on the list of probable causes."

The Search For Relief

Increasingly, Caleb's truncal contractions were becoming debilitating. The first doctor he saw prescribed oxcarbazepine (Trileptal), an antiseizure drug normally given to prevent convulsions in people with epilepsy. The drug was effective in stopping the truncal contractions for a time. But the effects eventually wore off, and his doctor was reluctant to increase the dose because of the risk of side effects.

Caleb began to develop problems in his hips, hands, and arms. He could still walk and write, but both walking and writing were tiring because so many additional muscles were contracting at the same time.

"Dystonia is not so much a problem with turning on muscles as turning off muscles," Dr. Mink explains. "People with generalized dystonia can [perform fine motor movements] such as pinch things with their thumb and forefinger, but these movements activate muscles that act on their wrists and their elbow and maybe even their shoulder. So while they're pinching they're getting lots of excessive muscle contraction. This can make simple tasks difficult, sometimes impossible, and with opposite muscles contracting at the same time you can get a twisting motion. Untreated, this twisting and contracting can shorten and even snap tendons and lead to permanent physical damage."

Through their research into Caleb's symptoms, the Metherells learned about the Dystonia Medical Research Foundation (DMRF). It was at about this time that they met Dr. Mink, and he suggested they take the genetic test for DYT1 dystonia at the Cleveland Clinic.

The Diagnosis Raises More Questions

Caleb's mother recalls the moment she heard that Caleb had tested positive for DYT1 dystonia. "It was a bittersweet moment," she says. "It was like, yes, we finally have a diagnosis, but it wasn't one we wanted to hear."

Delivering the diagnosis is not always easy, Dr. Mink acknowledges. "It is a difficult conversation because there is a lot of uncertainty about the condition. If I have a child whose foot turns in and I diagnose DYT1 dystonia, I can't tell his family for sure that it's always going to be just the foot or that it's going to spread to other body parts. It's frustrating for families when I say I don't know what is going to happen; either it's going to worsen or it's not. That's kind of unsatisfying if you're a parent."

The rate of progression is hard to predict, Dr. Mink says. "The most rapid progression is usually in the first five years after symptoms begin, and then most people reach a plateau and become relatively stable at that point. But it's hard to predict where it will end and how long it will take to get to that point." Because it is an inherited disease, Dr. Mink says, "I see siblings who have very different rates of progression and different patterns of involvement of their body."

DYT1 dystonia is an autosomal dominant inherited condition, which means that a person has to inherit only one mutated gene from one parent to be at risk for the condition. Yet only about one-third of people with the mutated gene go on to develop any symptoms of dystonia.

Why two-thirds of people with the mutation show no signs of dystonia is a mystery, Dr. Mink says. The most prevalent theory is that the gene mutation makes a person susceptible or predisposed to the condition, but some other precipitating factor causes the symptoms. Researchers have looked at viruses, other genetic and environmental factors, and even social situations, without finding a specific cause.

What is more certain, Dr. Mink says, is that treatment options are improving and researchers have gained a better understanding of the disease in the last five to 10 years.

"I think we're going to continue to see improvements that will lead to more uniformly effective treatments," Dr. Mink says. "I paint a picture of hope because this is not a fatal disease, nor is it a degenerative disease. There are things we can do to help."

Treatments That Help

Botulinum toxin (Botox) is the only drug approved by the U.S. Food and Drug Administration for dystonia. It is most effective for focal dystonias—those that affect a single body part such as the eye (blepharospasm) or hand (writer's cramp).

"Botulinum toxin has been a godsend for some of the focal dystonias, but not for these generalized dystonias," which affect multiple parts of the body, says Mahlon DeLong, MD, a professor of neurology at Emory University in Atlanta, who is also the scientific director of the Dystonia Medical Research Foundation and a member of the AAN. "At this point, the drugs that we have are inadequate for the generalized forms."

There are other medications that doctors prescribe, but some patients benefit from them and others don't.

"It's not uncommon for us to start a new medicine and have a lot of hope because the child seems to respond quite well, but then they don't seem to respond anymore," Dr. Mink says. "This can be quite frustrating for children and their families."

Caleb was prescribed an antiseizure drug in combination with baclofen, a muscle relaxant, to relieve his truncal movements. After that combination was no longer helpful, he was prescribed trihexyphenidyl (Artane) to treat the stiffness, tremors, and spasms. But he began to experience mental fogginess—a side effect associated with the drug—so he is now being weaned off of it.

A Surgical Procedure Offers Hope

When the dystonia involves the whole body—what is referred to as generalized dystonia—deep brain stimulation (DBS) is an option, Dr. Mink says. The family is now considering that option for Caleb.

DBS entails surgery to place four electrodes in a part of the brain called the basal ganglia, which is part of the brain's motor circuit. The electrodes are connected to a pacemaker-like device that is inserted into a cavity in the chest. The device sends electrical signals to the brain. Exactly how it works is unknown, but neurologists speculate that the electrical stimulation disrupts, cancels, or corrects the errant and excessive neuron firings that instruct the wrong muscles to contract.

DBS was first used in Parkinson's disease, a disorder characterized by difficulty turning muscles on, and later for generalized dystonia, a condition that triggers abnormal movement because the body has difficulty shutting muscles down.

Caleb and his parents are most concerned about whether it will work for their son and whether the risks of a surgical procedure are worth taking. The DMRF referred them to a family in which three out of four children were diagnosed with and developed the symptoms of DYT1 dystonia. Two of the children underwent DBS as adults, and they believe that they have received tremendous benefit from it.

"For certain forms of dystonia, and DYT1 is probably the best example, DBS can be dramatically effective," Dr. Mink says. Both he and Dr. DeLong estimate that if the patient is chosen properly and the surgery is performed by an experienced team, about 80 percent of patients see significant benefit. "There's a 1 percent chance that patients will have a complication with bleeding, which is the thing we are most concerned about," Dr. DeLong says. "Infection is always a possibility, but relatively speaking, this is a safe procedure and the benefit is enormous for these patients."

Both neurologists have seen very disabled and wheelchair-bound patients walk and function with little or no signs of dystonia after the DBS operation. The symptoms of the disorder appear to be reversible if caught before physical damage is permanent, and there is some evidence that younger patients get the most benefit from it.

Dr. Mink adds that 20 percent of patients do not experience significant benefits. Because the expectations are so high, he says, a poor result can be very disappointing.

So Caleb and his parents are facing a difficult decision. "We bounce every idea off of Caleb and let him have a voice in his care," Caleb's dad says. "Up to this point he has not been too interested [in DBS], but more recently he started to express interest.

"None of the medicines have helped with his vocal dystonia, and I want him to have a voice and to be able to socialize and talk on the phone with friends and family and to be able to sing. I want him to be able to run and ride a bike with his friends and play sports and just enjoy being a kid," he adds.

The Metherells are thankful for the support they have received from their friends, the DMRF community, and Dr. Mink. As for Caleb, he approaches his condition—and the road ahead with grit and hope.

For now, the 12-year-old uses a wheelchair to get around and has an aide helping him take notes and make his way to different classrooms in school. Caleb has very little use of his left arm and hand and cannot write with his right hand anymore. He finds it difficult to speak, and it is hard for people to understand him. Luckily, his younger brother and best buddy, Josh, understands much of what he is saying and is an eager translator. Even as Caleb becomes more disabled by the symptoms, he plays down his disability.

"If I spoke to a kid who was just diagnosed with dystonia, I would say not to worry or think of the bad stuff, because if you do that you'll have not much of a good day. I would also say that if you stay positive and think on the bright side, like me, you will have a good day.

"Dystonia affects almost everything, and it makes it so I sometimes move uncontrollably," he adds, "and that is pretty much it."

The other Dystonias

• Cervical dystonia (spasmodic torticollis): A type of dystonia that affects the neck muscles. It can create problems with turning the head and neck from side to side.
• Blepharospasm: This type of dystonia causes involuntary contraction of the eyelids. It can cause the eyelids to close involuntarily and for indefinite periods of time.
• Oromandibular dystonia: A dystonia of the jaw, lips, and/or the tongue. It can make eating and swallowing very complicated because the jaw may be held open or shut for periods of time.
• Spasmodic dysphonia: A dystonia of the vocal cords. It can cause symptoms such as speech that wavers, speech that sounds like a whisper, or speech that is hesitant.
• Writer's cramp (occupational dystonia): A dystonia that affects the muscles of the hand and forearm. It is triggered by attempting to write or execute other fine-motor hand functions.

Source: The National Institute of Neurological Disorders and Stroke (NINDS)

For More Information:

• Dystonia Medical Research Foundation
• Dystonia Society
• Dystonia: The Basics