One in every 2,500 people is born with Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuromuscular disorder that afflicts more than 2.5 million people worldwide – approximately as many as suffer from multiple sclerosis.
Los Altos resident Elizabeth Ouellette learned 10 years ago that CMT has nothing to do with teeth.
Ouellette emigrated from France to the Bay Area with her husband, Gilles Bouchard, and son Yohan, then 3 years old. A fairly typical toddler, Yohan was walking – but he was navigating on his tiptoes.
“We knew intuitively there was something wrong,” Ouellette said.
A pediatric exam uncovered tight muscles in the Achilles’ heels, and the doctor recommended physical therapy. Three years later, when a pediatrician discovered Yohan had no deep-tendon reflexes, he recommended that Yohan see a pediatric neurologist.
Dr. John Sum diagnosed CMT through a DNA blood test when Yohan was 7. Although there are 40 types of CMT, Sum discovered the needle in the haystack after one test – the most common form, CMT1A. The diagnosis of an obscurely known disease and its type answered some questions about Yohan’s symptoms but offered no hope.
“There are no treatments and no cures,” Ouellette said. “And it’s progressive.”
Living to learn
The Oullette-Bouchard family would learn much about CMT in the ensuing months, but it wouldn’t be through local support groups – there weren’t any for Charcot-Marie-Tooth. Because CMT affects the nerves, doctors suggested a muscular dystrophy support group, which couldn’t offer much information on Yohan’s affliction.
Three years later, Ouellette learned of the Charcot-Marie-Tooth Association, a non-profit organization founded in 1983 to support patients and family, educate the public and promote research for treatments and a cure.
Discovered in 1886 by three physicians – Jean-Martin Charcot, Pierre Marie and Howard Henry Tooth – the disease is a progressive deterioration of the peripheral nerves that control sensory information and muscle functions of the lower leg, foot, hand and forearm. It crosses all racial, ethnic and geographic borders.
In layman’s terms – the duplication of the gene in CMT1A prompts an overproduction of protein that causes the deterioration of myelin, the insulation surrounding nerve fibers. As the myelin deteriorates, exposing the nerve fibers, those begin to deteriorate as well, resulting in nerve impulses no longer able to transmit efficiently.
The disease can affect reflexes and the feet – bone abnormalities, high arches, hammertoes – and contribute to muscle loss, balance problems, decreased hand function and clawed fingers, arm- and leg-muscle cramping, spine curvature and, at times, breathing difficulties.
First symptoms include leg weakness, frequent tripping and loss of balance. Anyone whose parent has CMT has a 50 percent chance of inheriting the disorder, which may not be diagnosed until well into middle age. The severity of the disease varies greatly, even among those in the same family with the same type of CMT.
“(Doctors) don’t understand why,” Ouellette said. “It’s just the way it is.”
What perplexed Oullette and her husband was that neither has CMT – nor does anyone in the family. Yohan’s disease was caused by an inexplicable, spontaneous mutation of a gene now encoded in his own DNA.
“For Yohan, there will be a 50-50 chance his children will have CMT,” she said.
Ouellette dove into the association’s mission to educate the health-care community and the public – and, more importantly, to help support the growing numbers affected by the disorder, expanding national support groups from 16 to 50 across the country; establishing a local support group that meets quarterly at the Los Altos main library; convening a CMT summit in Palo Alto for patients, family and health-care providers; and accepting a position on the association’s board of directors.
Sept. 19-25 marked a coup for Ouellette and CMT – the first CMT Awareness Week. After a visit to Congress, Ouellette hopes to convince legislators that September should be CMT Awareness Month.
Learning to live
A mere 7 years old, Yohan was equally confused about doctors’ CMT diagnosis.
“At first, no one knew what to do with it,” Yohan said. “They told us it would just go away.”
But CMT doesn’t go away, though physical therapy, corrective orthopedic surgery, leg braces and other devices can alleviate symptoms. Still, no one warned Yohan that classmates could be so cruel.
Yohan’s years at Oak School were filled with taunts and humiliations inflicted by fellow students. Prone to tripping often and slower on his feet than others, his peers didn’t understand that he was challenged by a debilitating disease.
“It was brutal,” said Yohan, now 17. “I couldn’t do all the physical activities.”
Ouellette visited the school to make a special presentation on CMT so that children would understand the disease and what Yohan was experiencing. Their attitudes changed – “People apologized,” he said.
Now enrolled as a junior at Palo Alto Preparation High School, Yohan loves English, history and math (calculus, mind you), enjoys computers, archery and soccer – “I try to play every day” – and challenges competitors in the popular trading-card game Magic: The Gathering. Shelves lined with books in his room attest to late nights of reading.
While he tries not to let CMT limit his activities, Yohan continues to suffer from the disease’s effects – tiredness, sleep apnea, heat intolerance and hand tremors.
“My handwriting’s pretty bad, but I’m pretty lucky,” he said. “Some people can’t grip and can’t write.”
He also can’t stand for long periods of time, which makes his small school an ideal place for him in moving from class to class – along with its flexibility.
“I have lots of doctor appointments,” Yohan said. “Otherwise, I try not to think about (CMT).”
A STAR is born
In 2008, the association launched Strategy to Accelerate Research (STAR) to fund the CMT-related studies of international researchers searching for understanding and a cure for the disease.
Because scientists have identified CMT’s causes and pinpointed more than 33 gene defects associated with the disorder, it has become easier to replicate lab models to develop treatments, test the effectiveness of available medications, experiment with other medications and test possible cures.
But it’s the association’s team-effort strategy that enables communication among separate research groups, Oullette said.
“We have a medical advisory board to help the collaboration,” she said. “It’s more like a business program – and it’s working.”
Oullette said the National Institutes of Health is sharing its compound laboratory with CMT researchers, who have already identified several FDA-approved drugs for other diseases that show promise in treating CMT.
With the automated testing accomplished by robots, which is speeding up research, scientists are tickling the interests of pharmaceutical companies.
“This is the most hopeful time for families with CMT,” Oullette said. “Now we’re working with drug companies to use their libraries.”
To date, researchers have identified two potential medications for CMT – vitamin C and onapristone – as effective in reducing the proteins that attack the myelin.
“It sounds like they’ll discover a cure in my lifetime,” Yohan said.
But Yohan and his family aren’t waiting for a cure in order to seize the day – he has an impressive list of countries he has visited, with upcoming travels planned to Spain, Portugal and Morocco.
“Why not live in the moment?” Ouellette asked. “That’s what Yohan has taught us.”