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Open Access Research

Early presentation of gait impairment in Wolfram Syndrome

Kristen A Pickett12, Ryan P Duncan1, James Hoekel3, Bess Marshall46, Tamara Hershey257, Gammon M Earhart128* and And the Washington University Wolfram Study Group

Author Affiliations

1 Program in Physical Therapy, Washington University in St. Louis, Campus Box 8502, 4444 Forest Park Blvd, St. Louis MO 63108, MO, USA

2 Department of Neurology – Movement Disorders Section, Washington University School of Medicine, St Louis, MO, USA

3 Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO, USA

4 Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA

5 Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

6 Department of Cell Biology, Washington University School of Medicine, St Louis, MO, USA

7 Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA

8 Department of Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO, USA

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Orphanet Journal of Rare Diseases 2012, 7:92  doi:10.1186/1750-1172-7-92

Published: 8 December 2012

Abstract

Background

Classically characterized by early onset insulin-dependent diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological abnormalities, Wolfram syndrome (WFS) is also associated with atypical brainstem and cerebellar findings in the first decade of life. As such, we hypothesized that gait differences between individuals with WFS and typically developing (TD) individuals may be detectable across the course of the disease.

Methods

Gait was assessed for 13 individuals with WFS (min 6.4 yrs, max 25.8 yrs) and 29 age-matched, typically developing individuals (min 5.6 yrs, max 28.5 yrs) using a GAITRite ® walkway system. Velocity, cadence, step length, base of support and double support time were compared between groups.

Results

Across all tasks, individuals with WFS walked slower (p = 0.03), took shorter (p ≤ 0.001) and wider (p ≤ 0.001) steps and spent a greater proportion of the gait cycle in double support (p = 0.03) compared to TD individuals. Cadence did not differ between groups (p = 0.62). Across all tasks, age was significantly correlated with cadence and double support time in the TD group but only double support time was correlated with age in the WFS group and only during preferred pace forward (rs= 0.564, p = 0.045) and dual task forward walking (rs= 0.720, p = 0.006) tasks. Individuals with WFS also had a greater number of missteps during tandem walking (p ≤ 0.001). Within the WFS group, spatiotemporal measures of gait did not correlate with measures of visual acuity. Balance measures negatively correlated with normalized gait velocity during fast forward walking (rs = −0.59, p = 0.03) and percent of gait cycle in double support during backward walking (rs = −0.64, p = 0.03).

Conclusions

Quantifiable gait impairments can be detected in individuals with WFS earlier than previous clinical observations suggested. These impairments are not fully accounted for by the visual or balance deficits associated with WFS, and may be a reflection of early cerebellar and/or brainstem abnormalities. Effective patient-centered treatment paradigms could benefit from a more complete understanding of the progression of motor and other neurological symptom presentation in individuals with WFS.

Keywords:
Wolfram Syndrome; Gait; Ataxia; Development