Facioscapulohumeral muscular dystrophy

Leiden University, Leyden, South Holland, Netherlands
Muscle & Nerve (Impact Factor: 2.28). 07/2006; 34(1):1 - 15. DOI: 10.1002/mus.20522


Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly inherited disorder with an initially restricted pattern of weakness. Early involvement of the facial and scapular stabilizer muscles results in a distinctive clinical presentation. Progression is descending, with subsequent involvement of either the distal anterior leg or hip-girdle muscles. There is wide variability in age at onset, disease severity, and side-to-side symmetry, which is evident even within affected members of the same family. Although FSHD is considered a relatively benign dystrophy by some, as many as 20% of patients eventually become wheelchair-bound. Associated nonskeletal muscle manifestations include high-frequency hearing loss as well as retinal telangiectasias, both of which are rarely symptomatic. The causal genetic lesion in FSHD was described over a decade ago, raising hope that knowledge about its molecular and cellular pathophysiology was soon to follow. In the vast majority of cases, FSHD results from a heterozygous partial deletion of a critical number of repetitive elements (D4Z4) on chromosome 4q35; yet, to date, no causal gene has been identified. The accumulating evidence points to a complex, perhaps unique, molecular genetic mechanism. The absence of detectable expressed sequences from D4Z4, the association of FSHD-causing 4q35 deletions with a specific distal genomic sequence (4qA allele), altered DNA methylation patterns on 4q35, as well as other direct and indirect evidence point to epigenetic mechanisms. As a consequence, partial deletion of D4Z4 results in a (local) chromatin change and ultimately results in the loss of appropriate control of gene expression. There is at present no effective treatment for FSHD. A better understanding of the underlying pathophysiology is needed to design targeted interventions. Despite these limitations, however, two randomized controlled clinical trials have been conducted on FSHD. These trials, along with a previous natural history study, have helped to better define outcome measures for future trials in FSHD as well as other dystrophies. Muscle Nerve, 2006

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    • "With an incidence between 1:15,000 and 1:20,000 FSHD is the third most common myopathy. [7] [8] The age at disease onset ranges from infancy to middle age with the majority becoming symptomatic in the second and third decade of life. [9] Nowadays, no therapy is available for FSHD. "

    Full-text · Article · Nov 2015
    • "A generally slowly progressive disease, FSHD causes significant lifetime morbidity, with up to 20% of those above age 50 requiring full time wheelchair use. FSHD has a distinct regional distribution of muscle weakness at onset [7]. Non muscular involvement in FSHD including hearing loss and retinal vascular disease is infrequent and restricted to patients with the most severe disease [8] [9]. "

    No preview · Article · Nov 2015 · Neuromuscular Disorders
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    • "Since a loss of trunk stability cannot readily be resolved, an important clinical implication of our results seems to be that residual ankle plantarflexion power should be optimally preserved in patients with FSHD. Since many patients are prescribed anklefoot orthoses (AFOs) for the compensation of drop foot [32], maximal effort is warranted to support ankle dorsiflexion while maintaining the possibility to plantarflex the ankle joints during walking. This approach would imply the use of dynamic AFOs with a spring-like dorsiflexion support, allowing active plantarflexion during push-off. "
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    ABSTRACT: Facioscapulohumeral muscular dystrophy is a slowly progressive hereditary disorder resulting in fatty infiltration of eventually most skeletal muscles. Weakness of trunk and leg muscles causes problems with postural balance and gait, and is associated with an increased fall risk. Although drop foot and related tripping are common problems in FSHD, gait impairments are poorly documented. The effect of ankle plantarflexor involvement on gait propulsion has never been addressed. In addition to ankle plantarflexion, gait propulsion is generated through hip flexion and hip extension. Compensatory shifts between these propulsion sources occur when specific muscles are affected. Such a shift may be expected in patients with FSHD since the calves may show early fatty infiltration, whereas iliopsoas and gluteus maximus muscles are often spared for a longer time. In the current study, magnetic resonance imaging was used to assess the percentage of unaffected calf, iliopsoas and gluteus maximus muscles. Joint powers were analyzed in 10 patients with FSHD at comfortable and maximum walking speed to determine the contribution of ankle plantarflexor, hip flexor and hip extensor power to propulsion. Associations between muscle morphology, power generation and gait speed were assessed. Based on multivariate regression analysis, ankle plantarflexor power was the only factor that uniquely contributed to the explained variance of comfortable (R(2)=80%) and maximum (R(2)=86%) walking speed. Although the iliopsoas muscles were largely unaffected, they appeared to be sub-maximally recruited. This submaximal recruitment may be related to poor trunk stability, resulting in a disproportionate effect of calf muscle affliction on gait speed in patients with FSHD. Copyright © 2014 Elsevier B.V. All rights reserved.
    Full-text · Article · Dec 2014 · Gait & Posture
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