Spotlight on Research: Charcot-Marie-Tooth Disease

Categories: Orthopedics Now, Patient Families

Researchers Shine Light on Charcot-Marie-Tooth Disease

Sylvia Ounpuu & Kristan Pierz - Charot-Marie-Tooth Research - Ortho Now Summer 2017
Sylvia Õunpuu, Director of Research at Connecticut Children’s Center for Motion Analysis (left), reviews research findings with CMA Medical Director Kristan Pierz, MD. (Photo Credit: Erin Blinn-Curran)

Research on a century-old disease continues at Connecticut Children’s Medical Center, where researchers are working to unlock the mysteries of Charcot-Marie-Tooth (CMT) disease, a relatively rare condition but one of the most commonly inherited neurological disorders observed in children and youth.

First identified in 1886, CMT – also known as hereditary motor and sensory neuropathy – affects 1 in 2,500 people in the United States and comprises a group of disorders that damage the peripheral nerves that carry signals from the brain and spinal cord to the muscles. CMT causes muscle weakness and deterioration, as well as loss of sensation in the feet and lower legs, hands and forearms. While not fatal, the disease is variably progressive.

“Charcot-Marie-Tooth disease tends to run in families and tends to affect the feet more than hands,” said Kristan Pierz, MD, an orthopedic surgeon and Medical Director of Connecticut Children’s Center for Motion Analysis (CMA) in Farmington, where comprehensive assessments of gait abnormalities are carried out. “Progression of symptoms is gradual and can affect patients differently. Symptoms can range from subtle to severe,” Dr. Pierz said.

Onset of the disease may occur any time and may include weakness of the foot and lower leg muscles, resulting in foot drop and a steppage (high-stepping) gait leading to frequent tripping or falls. Foot deformities, such as high arches and hammertoes (a deformity of one or both joints of the toes), are also common characteristics and can affect a patient’s ability to walk.

Forefront of Research

While knowledge about Charcot-Marie-Tooth disease is still considered to be in its infancy, Connecticut Children’s is at the forefront of CMT research.

“We started our local research efforts in motion analysis in 2011 and published our first paper on a retrospective review of gait function in 2013,” said Sylvia Õunpuu, a Connecticut Children’s kinesiologist and Director of Research at the CMA. “We have since published two other chapters on gait function and proposed treatment options based on gait patterns.”

“Our biggest contributions to date are classification of gait function with a focus on the ankle in CMT; documentation of preliminary treatment outcomes for orthopedic surgery; and documentation of bracing outcomes,” she said.

Two ongoing studies include a postoperative analysis in children with CMT who have had surgery, and a study that tracks the natural history of gait decline in patients who have not.

The Center for Motion Analysis has been collecting motion data on pediatric patients with CMT disease since 2004, allowing researchers to look at data retrospectively.

“The long-term goal is to provide evidence-based criteria for surgical intervention for kids with CMT,” Õunpuu said.

CMT Center of Excellence

In addition to running a CMT Multispecialty Clinic for patients and families, Connecticut Children’s was named a Pediatric Charcot-Marie-Tooth Center of Excellence in 2016. Designated as a Clinical Center of Excellence by the Inherited Neuropathy Consortium (INC), supported by the National Institutes of Health, the Center is led by neuromuscular specialist Gyula Acsadi, MD, PhD, Division Head of Neurology and Rehabilitation, who diagnoses pediatric patients with CMT.

Dr. Acsadi sees approximately 40 patients with CMT at Connecticut Children’s each year, while the Center for Motion Analysis sees about 10. The designation as a CMT Center of Excellence is significant because it reflects both high-level patient care and research.

According to Dr. Acsadi, there are 20 such Centers of Excellence in the worldwide consortium, including only five pediatric centers. Connecticut Children’s is one of only three gait labs involved in research by this Consortium.

“The INC is a worldwide group that is gathering a minimal data set, which is a standardized set of natural history measures, across sites and storing the information collected in a central database,” Õunpuu explained. “The database is then available for all members to access for research purposes. The members also collaborate on treatment protocols, which allows for greater patient numbers and, therefore, better statistical significance to prove research findings.”

“When you are part of a clinical trial, the patients know that they get access for the most advanced treatments.,” Dr. Acsadi noted. “We have patients from other states receiving care and participating in our research.”

What is unique is that Connecticut Children’s CMT Center of Excellence utilizes a state-of-the-art gait analysis to aid bracing and surgical treatments, if needed.


Foot Work

CMT is a group of inherited disorders that affect the peripheral nerves, located outside the brain and spinal cord. According to the Charcot-Marie-Tooth Association, there are 90 kinds of CMT and each is caused by a different kind of mutation, with more causes being discovered every year.

“Patients can definitely have different presentations of CMT,” Dr. Pierz said. “Emma had foot deformities with painful high arches and claw toes that are often seen in patients with CMT.” Gonsalves underwent whole-foot reconstruction to fix her bent toes and plantar fasciitis, one of the most common causes of heel pain.

“It was a long recovery, but my toes are now permanently straight,” Gonsalves said. “I walked barefoot for the first time this year.”

Importance of Follow-Up

“CMT is a progressive disorder, so following patients over time is important,” Dr. Pierz said. “The Center for Motion Analysis offers objective data that can truly guide treatment decision-making. One treatment that isn’t appropriate at one point in time may become appropriate over a few years. Tracking patients with objective data will lead to better decision making. X-rays and physical exams in the office are not nearly as useful as full-motion data when evaluating function,” she explained.

While adults typically end up seeing foot and ankle specialists, Dr. Pierz said she looks forward to expanding care to older patients. “We have seen parents and their children with CMT in the Center for Motion Analysis, and the data is interesting,” she said.

Gonsalves, who says she can now wear regular shoes again, returns to the CMA at least once a year to meet with Dr. Pierz.

“She has completely made my life so much better,” Gonsalves said. “She has given me hope. I think she is helping me be the best person I can be.”

Reviewing Video - Center for Motion Analysis
Center for Motion Analysis (CMA) Medical Director Kristan Pierz, MD (left), and Sylvia Õunpuu, CMA Director of Research, review early videos of long-time patient Emma Gonsalves. (Photo Credit: Erin Blinn-Curran)

Research at the Center for Motion Analysis relies heavily on donor support for its research activities. Visit our Make a Gift page to support research, including that for Charcot-Marie-Tooth disease. (Under Gift Designation click “Direct my gift to/Other”, highlight “Other” and where prompted, please type in ‘Center for Motion Analysis’.)