CMT Researchers Tell Their Own Story

by Margaret Wahl on July 1, 1994 - 11:26am

Dr. Phillip Chance, 41, associate professor of neurology and pediatrics at the University of Pennsylvania, and Dr. Jim Lupski, 37, associate professor at Baylor College of Medicine's Institute for Molecular Genetics, have a lot in common as major players in MDA's genetics research in Charcot-Marie-Tooth disease.

But until recently, few people knew that Chance and Lupski have something else in common: They both have CMT, a disease of peripheral nerves that causes gradual loss of strength and sensation in the feet, ankles and sometimes hands.

Dr. Jim Lupski, left, and Dr. Phillip Chance know what people with CMT experience.

Chance says patients and their parents feel "a little less weird" and a little less angry when they discover their doctor has a neuromuscular disease.

Chance, who wears ankle-foot braces (invisible under long pants), is now more bothered by weakness and lack of dexterity in his hands than by difficulty walking, but he hasn't forgotten what grief his foot problems caused him as a teenager.

Growing up in Memphis, Tenn., one of two boys in a family where the "emphasis was on the physical," wasn't easy. Chance was never athletic and wasn't much interested in the hunting and fishing trips his family and friends took. Electronics and music captured his imagination more, even before signs of CMT appeared. "I was always considered different," he says, "and the CMT just confirmed it."

Chance stumbled and fell frequently, and parents and teachers told him to pick up his feet. "I don't think people's first notion was that it was a medical problem," he says. "They thought it was a behavioral manifestation." The family doctor offered reassurance that nothing was really wrong.

Finally, some answers

At 14, Chance was referred to an orthopedic surgeon by his high school physics teacher.

There followed a battery of painful and probably unnecessary tests, he recalls, but a diagnosis of CMT was finally made.

Unfortunately, "the matter was then dropped. They told my parents it was a genetic disease, and no follow-up appointments were made."

He reflects that a referral to the MDA clinic in Memphis might have put him in touch with the right doctors and with fellow CMT patients, as well as given him braces that would have allowed a normal gait throughout his adolescence.

Even in medical school, people didn't say much, says Chance, although some assumed he had polio as a child. On the other hand, he never talked about his condition, so he believes people may have decided he wanted to be left alone.

A change of outlook

Although he used to hide his condition from patients and colleagues, Chance says he's now more open about it, acknowledging that it has a "very powerful effect" on patients.

"I've softened on the [privacy issue] as I've gotten older," Chance says. Although the disease cost him a career as a professional clarinetist and made for many unhappy moments in high school, Chance is now grateful for his relatively good health. "There's no heart disease or cancer in my family," he says, "so I've begun to put CMT into perspective."

He always asks his pediatric patients whether they're being teased in school. "I tell them, 'It won't be many more years before it won't matter. Once you're an adult, it won't matter so much.'"

All in the family

Jim Lupski had a somewhat better experience, despite 11 surgeries on his feet and ankles between 15 and his second year of college.

Lupski grew up with seven siblings in Hicksville, N.Y., and wasn't the first in the family to have CMT. (Eventually, four of the eight children developed it.)

His older brother Tom started having trouble walking when he was about 10 and was found to have CMT after his condition was mistakenly diagnosed as Duchenne muscular dystrophy, a much more serious disease.

When Lupski began twisting his ankles and having trouble walking at age 13, his parents already knew what to expect. They took him to the same orthopedic surgeon who had seen his brother Tom. "One week later," Lupski says, "I found myself in the hospital." For an active boy who had played junior high school football, it was a shock.

Advantage of disadvantage

Both feet were in casts for six months, and Lupski was in a wheelchair and out of school. Because of several later surgeries, he missed his sophomore and junior years of high school and was tutored at home a few hours a day. "I think it was an advantage," he says. "I developed independent study habits."

Among the books Lupski read in high school were James Watson's The Double Helix (about discoveries in genetics) and William Nolen's The Making of a Surgeon. "Genetics fascinated me," he says. However, because he wasn't in school, he wasn't able to do any lab work. "I didn't dissect anything until I was in medical school."

With seven siblings in the house and friends who came to visit, Lupski didn't feel isolated, although he admits he was frustrated being in a wheelchair and wasn't always "the most pleasant person to have around." He returned to school in his senior year.

Although unable to play high school sports, Lupski learned to drive the summer before his senior year and danced at his senior prom. He continued to excel at academics, particularly the sciences. Lupski's hands had never been much affected by CMT, and he didn't see any barrier to becoming a doctor.

His surgeon became a friend and role model who encouraged him to go into medicine. "The human side of medicine has always been very important to me — how to take care of patients," Lupski says. He has a doctoral degree in biochemistry and molecular biology and an M.D. At Baylor, Lupski heads the physician-scientist, or M.D.-Ph.D., program.

A later mentor for Lupski was Dr. Carlos Garcia, an MDA clinic director in Louisiana. "Carlos had incredible physician-patient relationships," Lupski says. "If Carlos said something, they listened."

On the CMT gene trail

Lupski confers with colleague Dr. Kent Anderson.

In 1987, shortly after Lupski arrived at Baylor, he and Garcia began recruiting CMT families on weekends to help with their CMT gene search. "It was as important in the early days to collect data from people without the disease as with it," Lupski says. Garcia was able to persuade all the members of a large Cajun family to be tested, including blood drawing and uncomfortable nerve conduction tests.

"We got incredible cooperation," Lupski recalls. "I'd stick them, Carlos would 'electrocute' them, and they'd feed us this great Cajun food."

Chance and Lupski have made major contributions to CMT research. In 1991, Lupski and MDA researcher Pragna Patel identified a duplicated section of chromosome 17 that causes the most common form of CMT. In 1992, Chance and Lupski were among those who pinpointed a gene called PMP22 as the crucial gene involved in the duplicated segment.

In 1993, Chance identified how the DNA duplication occurs in the chromosome 17 form of CMT, citing a mechanism earlier suggested by Lupski. Later that year, Chance was on teams that identified genes on chromosome 1 and on the X chromosome that can also cause the disease.

So far, neither doctor has identified the gene involved in his own disease, although both have been tested.

Neither worries too much about having CMT in the family. Lupski has two daughters, 5 and 1, and Chance and his wife are planning to have children.

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