Facioscapulohumeral muscular dystrophy: a prospective study of weakness and functional impairment

Abstract

Only isolated prospective studies have attempted to chart the natural history of facioascapulohumeral muscular dystrophy (FSHD), a benign myopathy with notoriously variable clinical manifestations and progression. This 10-year prospective study was performed to document by simple clinical methods the natural history of 16 patients with moderately advanced FSHD. Limb strength was evaluated by the bedside manual muscle test. Global weakness was documented as a composite average muscle score (AMS). Limb function was evaluated by a non-linear grading system of important functional milestones. A scale of activities of daily living (ADL) was used to assess disability across multiple functional domains in a home environment. Six-monthly evaluations determined a linear deterioration of the mean AMS that reached statistical significance from baseline at the 5-year interval. Half of patients showed a functional decline of the arms by one grade. All patients maintained useful hand function. Three quarters of patients suffered functional decline of the legs, commonly by one grade. All patients remained ambulant. Interval analyses showed a linear deterioration of the mean ADL score that reached statistical significance from baseline at the 5-year interval. Functional deterioration was mostly due to impaired shoulder girdle activities. This study of a relatively homogeneous subgroup of FSHD patients showed a predictable rate of clinical progression in a muscle disease with a notoriously variable clinical presentation and outcome. Natural history data obtained in this study could serve as positive controls for future therapeutic trials in this patient population. The chosen clinical parameters proved useful tools for charting clinical disease progression. Functional tests proved advantageous, because decline was based partly on patient self-reports, thereby improving time and cost effectiveness.

Evidence-based guideline summary: Evaluation, diagnosis, and management of facioscapulohumeral muscular dystrophy

“…3 FSHD typically progresses slowly but variably. 4,5 About 20% of individuals with FSHD become wheelchair dependent after age 50. 1 Extramuscular manifestations occur in FSHD and can include respiratory compromise; retinal vascular disease that, rarely, leads to exudative retinopathy and visual loss; hearing loss; and, possibly, increased incidence of cardiac arrhythmias.…”

Whole‐body magnetic resonance imaging evaluation of facioscapulohumeral muscular dystrophy

“…Even clinical measures of function and patient‐reported outcomes can be confounded heavily by factors that are not related to the disease . Functional measurements, such as the 6‐minute walk test, may also change too slowly over the course of a disease to be useful in most clinical trials . Thus, identification of responsive and reproducible biomarkers is a major unmet need in muscular dystrophy research.…”

Risk of functional impairment in Facioscapulohumeral muscular dystrophy

“…Substantial variability exists in weakness between patients and within affected members in a single family. Progression of disease has been described in a large 3‐year natural history study and another smaller longitudinal study . Patients experience a slow loss of strength between 1 and 4% per year using composite strength scores.…”