Study Investigators: Sylvia Ounpuu, MSc; Gyula Acsadi, MD, PhD; and Kristan Pierz, MD

Background

The overall goal of this research is to improve treatment outcomes that address gait dysfunction (difficulty with walking patterns) in children with Charcot-Marie-Tooth disease (CMT). Walking ability is one of the most important factors for quality of life for people with CMT, and a better understanding of the relationship between gait function, community activity levels, and how these measures change over time is essential. Identifying biomarkers (measurable indicators of disease state or progression) is also important for evaluating the effectiveness of emerging treatments aimed at improving walking.

Thanks to generous funding from the Penn Medicine Orphan Disease Center, the research team was able to add 15 patient tests (some repeat assessments, some new participants) to their existing study cohort, which at the time of this report included 68 patients.

Results

A preliminary analysis focused on ankle motion in the sagittal plane (the forward-backward plane of movement) during walking, drawn from a cohort of 45 patients with CMT types 1 and 2, revealed differences in how ankle function changes with age depending on CMT subtype.

In children with CMT1, peak dorsiflexion (the upward bending of the foot toward the shin) during terminal stance (the point in the walking cycle just before the foot lifts off) increased with age through approximately 13 years (p=0.004) and then plateaued within the normal range (p=0.73). Peak ankle angle in mid-swing and in terminal stance were closely related (p<0.001), following a similar pattern of change with age.

In children with CMT2, there was no significant change in peak dorsiflexion during terminal stance with age (p=0.19), and peak ankle angle in mid-swing was not related to peak dorsiflexion in terminal stance (p=0.43) or to age (p=0.88). There were also no consistent age-related trends for individual patients who had multiple tests over time.

Summary

Children with CMT1 showed beneficial changes in ankle function during both the stance and swing phases of walking with age, reaching a plateau around age 13. Children with CMT2, however, did not show any systematic changes in ankle function during walking with age. Future studies with more repeat assessments for individual patients will be needed to better understand how gait changes over time in children with CMT.

The variability in gait and joint-level impairments across patients underscores the importance of understanding disease severity and progression at the individual level. This knowledge can support more informed treatment decisions and a clearer picture of how treatments perform in the context of ongoing disease progression.

HNF was pleased to fund this research at Connecticut Children’s Gait Lab. The project was led by Sylvia Ounpuu, MSc, Director of Research and Education, and Gyula Acsadi, MD, PhD, Division Head of Neurology. Both investigators are members of the Inherited Neuropathy Consortium, as is HNF.