P.167 Clinical outcome study of dysferlinopathy: gait analysis of siblings and phenotype variation

Abstract

Patients with limb girdle muscular dystrophy (LGMD) R2/2B, caused by mutations in the <i>DYSF</i> gene, have a distinct gait pattern, although this has not been characterised with instrumented gait analysis. In the Jain Foundation Clinical Outcome Study of dysferlinopathy (COS2, http://www.jain-foundation.org/dysferlinoutcomestudy), we are investigating the utility of instrumented gait analysis as a novel clinical biomarker. Patients with LGMDR2 have variability in the presentation of muscle weakness and rate of progression, even within family members. In a pair of siblings with LGMDR2, we conducted gait analysis at two points, six months apart when barefoot and shod. The aim was to quantify gait in siblings with LGMDR2 and evaluate temporospatial parameters changes over six months. Two COSII patients, a male aged 30, and his younger sister aged 27, completed gait analysis at baseline and six-month visits using an instrumented walkway (GAITRite, 240Hz). Patients were asked to walk at a comfortable walking speed when barefoot and shod, and to walk fast when shod only. Temporospatial characteristics including gait velocity, step length, step width, stance and swing duration were extracted. Barefoot gait velocities at baseline were similar between siblings with the male walking at 1.16m/s and his sister at 1.20m/s, however the male sibling walked with a step width double that of his sister. Functionally the male had a more severe disease presentation, with a North Star assessment for limb girdle type muscular dystrophy score of 28/54 at baseline, and the female 42/54. At baseline, both siblings had capacity to increase shod walking speed when asked to walk fast; by 25% for the male and 47% for the female sibling. At six months when shod, gait analysis determined very small changes (<5%) in walking speed, step length, stance time in both siblings. However, step width increased by 12% in the male subject. Gait analysis provides detailed evaluation of temporospatial parameters and captures differences across siblings and walking conditions.