Myotubular Myopathy
A dark past gives way to a bright future
by Dan Stimson
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When a baby is born with the muscle disease myotubular myopathy, the typical diagnosis is slow in coming, and when it finally arrives, it can be both frightening and misleading. That's what Gary and Pam Scoggin of Texas City, Texas, learned 11 years ago when their son John was born too weak to breathe on his own.
Doctors puzzled over John's condition for weeks until a geneticist, Gail Herman, recognized it as myotubular myopathy. She wasn't an expert on the disease, but after carefully consulting the available medical literature, she told Gary and Pam that John probably wouldn't live to see his first birthday.
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Though given a fatal prognosis at birth, John Scoggin grew to be a "neat kid" with a sharp intellect and a great sense of humor. |
Five years later, at Herman's request, John began sitting in on her lectures to medical students, as a shining example of how doctors can be wrong.
Today, "John has some bad things, but he's also got two parents that love him very much," says Pam Scoggin. "He loves to go to baseball games, and he's really into video games and just normal 11-year-old stuff."
Pam and Gary now run a resource group for families affected by myotubular myopathy. And Herman is carrying out a highly respected research effort to investigate causes -- and possible treatments -- for the disease.
Herman's research and the shared experience of families like the Scoggins are helping shape a new outlook for kids born with myotubular myopathy: Although the disease can cause death during infancy, many kids with the disease can live longer, more active lives than previously thought.
Strong Comeback
Myotubular myopathy (MTM) -- sometimes called centronuclear myopathy -- is an inheritable disease that causes a general lack of muscle strength and tone. There are three forms of the disease (see "Rare Forms"), and the type that John has is the most severe one, causing muscle problems at or before birth. It's called X-linked myotubular myopathy (MTMX) because it's caused by a genetic flaw on the X chromosome. (For that reason, only males develop the full-blown disease, while females can be unaffected carriers.)
John was born with the typical features of MTMX. The muscles of his trunk and limbs were so weak that his body was completely limp. The respiratory muscles in his chest couldn't power his lungs, and the muscles in his mouth and throat weren't strong enough for suckling or swallowing. Immediately after birth, he was placed on a ventilator and given a feeding tube.
Though most studies on MTMX suggested that John would soon die, he defied them all. At 9 weeks old, he underwent a tracheostomy (insertion of a tube in the trachea that sends air from a mechanical ventilator to the lungs) and a gastrostomy (insertion of a valve in the stomach for connection to a feeding tube, or g-tube).
As a toddler, he had his share of obstacles. He caught a few colds that turned into life-threatening respiratory problems. Weakness in his face and throat delayed his ability to speak, so he learned sign language to communicate.
Now that he's growing up, John is getting stronger. "In the past eight years, he's only stayed in the hospital once," reports his mother. He can speak softly, and he typically uses a ventilator only while he's sleeping. He uses an electric wheelchair to get around.
Like many kids with MTMX, John has above-average intelligence, and his fine motor skills are intact. He attends sixth grade at a regular public school -- where he makes straight A's in the gifted and talented program -- and he's a "whiz" at Nintendo.
"It's a wonderful reward to see how these kids can do things that no one expects them to be able to do," says Scoggin.
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Once too weak to sit up, Logan Beasley is now strong enough to walk with assistance from a Bronco gait trainer. |
Maria Beasley of Westminster, Mass., noticed the same trend in her son, Logan, born with MTMX three years ago.
"Doctors are totally amazed that Logan has come this far," says Beasley. "In the beginning, he couldn't hold his head up or do anything, but now he sits up alone very well by himself. He's definitely gotten much better."
Like John, Logan has a tracheostomy and a feeding tube, and uses a ventilator at night. He uses sign language to communicate, shares John's penchant for video games, and has a special appreciation of music and Shania Twain -- whom he calls his "girlfriend."
"He's just like any other 3-year-old. The only thing he can't do is get up and run," Beasley says.
A New View Emerges
The experiences of families like the Scoggins and the Beasleys are challenging the common view that MTMX means certain death. A recent MDA-funded study by Gail Herman, at the Children's Research Institute and Ohio State University in Columbus, is adding scientific weight to that challenge.
Herman's study, published last year in the Journal of Pediatrics, refutes the dismal view of MTMX that dominates the medical literature. Most previous reports indicated that boys with MTMX usually die within weeks or months of birth. But Herman found that of 55 boys with the disease, about two-thirds of them lived to be at least a year old.
And many are still living. "There are 10-, 12- and 14-year-old kids [with MTMX], and when you talk to them, they seem to have a good quality of life," says Herman. Some of these boys, she says, have relatively mild symptoms compared to those of John Scoggin and Logan Beasley.
For most of the children in her study, Herman believes that the use of ventilators to support respiratory function has made the critical difference. "I think kids with severe classic MTMX have a much better chance of surviving if they get a trach and a ventilator and a g-tube while they're still in the hospital," she says. Since some of the older studies were done, she points out, "We're much better at taking care of babies; we have better ventilators, more pediatric pulmonologists and better home care."
Use of a ventilator, she says, is especially important when a child with MTMX has a respiratory infection. "When they get a cold or pneumonia, many boys get so weak that they can't support their breathing," she says. While the most mildly affected boys in Herman's study don't use ventilators regularly, they do sometimes need them for combating respiratory illness.
Even with adequate ventilation and other forms of support, Herman acknowledges that there is still a significant number of families in which a child with MTMX doesn't survive. But her study provides hope for families by setting down scientific evidence for what the Scoggins and the Beasleys already knew -- with aggressive medical care, children with MTMX can survive.
Herman has noted a trend for many boys to get stronger, echoing the personal observations made by Scoggin and Beasley.
Herman's study appears to be having some impact among doctors. "I've gotten some calls where doctors saw the study and they call asking what to do -- or how to best support [kids with MTMX]," she says. She has hope that the disorder is being diagnosed more accurately, and that doctors are presenting the new information to families.
For more realistic, more encouraging information about MTMX, both Scoggin and Herman recommend that parents of children who've received recent diagnoses seek out other families with the disease.
"I always recommend that they should talk to other parents," says Herman. "You may get a little bit of a bias, but I think it's really important. If you hear about a 10-year-old boy who has [MTMX], that makes such a difference than just hearing that all these children die, or reading these awful things in the literature."
To help families with MTMX exchange information, the Scoggins founded a support group called the Myotubular Myopathy Resource Group. The group has a Web site (www.mtmrg. org), where families can share their personal experiences with MTMX.
Finding Better Ways to Care
By exchanging information, parents like Beasley have gained some ability to anticipate the course of MTMX in their children. More than that, they've learned better ways to care for their children, who typically have special medical needs beyond the use of a ventilator and a feeding tube.
For example, children with MTMX are prone to choking on mucosal secretions. In everyone, these secretions are produced in the lungs and expelled by way of the trachea; most people just swallow them down the esophagus without noticing. Because children with MTMX typically can't swallow or cough, the secretions can slide back down the trachea and block the passage of air. So, to prevent suffocation, children with MTMX often have their secretions dried up by medications or suctioned away regularly by a catheter through the tracheostomy (or both).
Because they lack the muscle tone required for postural support for sitting up, most children with MTMX develop scoliosis (curvature of the spine), sometimes requiring bracing or surgery. Many also experience weakness in muscles that control the focus and movements of the eyes, and movements of the eyelids. For that reason, John Scoggin can't blink and requires rewetting eyedrops every two hours.
To manage these health problems, parents depend partly on home nurses, says Scoggin. However, because most nurses lack familiarity with MTMX, parents must take the initiative in caring for the child, she says. They often learn the best methods of care by trial and error, or by talking to other parents.
For instance, when John Scoggin was younger, he sometimes had bouts of hypoventilation (difficulty breathing) that prompted Pam and Gary to drive him to the emergency room. Often, by the time they reached the hospital, John's breathing had returned to normal. Eventually, Pam and Gary realized that just setting John up in his car seat was helping him breathe by allowing better expansion of his lungs. "There are just little things like this that you have to learn the hard way," says Scoggin.
Scoggin has passed lots of advice on to other parents, and she and Beasley both say they've even taught health professionals some things about caring for kids with MTMX. "There are things that I've come up with," says Beasley, "where Logan's physical therapist has said to me, 'Oh, that's really good, I'm going to try that.'"
Motivating Discovery
Perhaps most important, the tireless efforts of parents like the Scoggins and Maria Beasley have contributed to the work of researchers like Gail Herman.
Fusion of Myoblasts
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Myotubes
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Muscle Fibers
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Early in muscle development, small mononucleate cells (cells with only one nucleus) called myoblasts aggregate and fuse together, forming large, tubular multinucleate cells. |
Within these cells, called myotubes, the nuclei are located near the center, and the protein-based machinery required for muscle contraction isn't fully formed. |
Normally, when a myotube becomes a mature muscle cell, or muscle fiber, the nuclei migrate to the cell's edges, and threadlike proteins organize into bundles that provide the force for muscle contraction. |
In MTM, some cells in affected muscles appear to get stuck at the myotube stage of development, interfering with contraction of the whole muscle. |
Prior to meeting the Scoggins, Herman conducted research broadly aimed at characterizing different X-linked genes. She wasn't specifically interested in the gene responsible for MTMX. But then, John Scoggin became a living contradiction of her understanding about MTMX, and over several years, he continued to impress Herman during regular office visits.
In the meantime, the Scoggins found 19 more children living with MTMX, and compiled information about them into a homemade book (which later became the basis for their Web site). "We sent the book to different hospitals and research agencies trying to find someone interested in doing research, because at that time, there was very little research being done," says Scoggin.
Scoggin says Herman "was amazed that we were able to find that many children, and said, 'I just can't ignore this. I'm going to write MDA to see if they'll give me the funding to do some research [on MTMX].'" The rest is both history and future.
Herman's 1999 study has not only shaken dire medical views about MTMX, it's also called attention to previously undocumented features associated with the disease.
Importantly, Herman found that boys with MTMX seem predisposed to health problems that aren't obviously related to muscle weakness. These problems include mild anemia, kidney stones, and various manifestations of gallbladder and liver dysfunction (including gallstones, jaundice and, more rarely, hemorrhaging of the liver).
During the study, Herman also noticed that boys with severe MTMX have typical physical features. For example, they tend to have a characteristic facial appearance, with a high forehead and long face, and a high-arched palate. They also tend to be tall for their ages.
Overall, Herman's observations suggest that MTMX not only affects muscles, but directly affects other tissues and organs as well. This discovery has significant implications for management and treatment of the disease.
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