Co-contraction of shoulder and upper extremity muscles in individuals with muscle dystrophy compared to healthy persons during reaching-to-target tasks.

On the basis of strong research evidence, Duchenne muscular dystrophy (DMD), the most common severe childhood form of muscular dystrophy, is an X-linked recessive disorder caused by out-of-frame mutations of the dystrophin gene. Thus, it is classified asa dystrophinopathy. The disease onset is before age 5 years. Patients with DMD present with progressive symmetrical limb-girdle muscle weakness and become wheelchair dependent after age 12 years. (2)(3). On the basis of some research evidence,cardiomyopathy and congestive heart failure are usually seen in the late teens in patients with DMD. Progressive scoliosis and respiratory in sufficiency often develop once wheelchair dependency occurs. Respiratory failure and cardiomyopathy are common causes of death, and few survive beyond the third decade of life. (2)(3)(4)(5)(6)(7). On the basis of some research evidence, prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone (not available in the United States), as a single morning dose is recommended for DMD patients older than 5 years, which may prolong independent walking from a few months to 2 years. (2)(3)(16)(17). Based on some research evidence, treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics has been reported to be beneficial in DMD patients with cardiac abnormalities. (2)(3)(5)(18). Based on expert opinion, children with muscle weakness and increased serum creatine kinase levels may be associated with either genetic or acquired muscle disorders (Tables 1 and 3). (14)(15)

Facioscapulohumeral dystrophy (FSHD) is a progressive muscle-wasting disease which leads to a decline in upper extremity functionality. Although the scapulohumeral joint's stability and functionality are affected, evidence on the synergetic control of the shoulder muscles in FSHD individuals is still lacking. The aim of this paper is to understand the neuromuscular changes in shoulder muscle control in people with FSHD. Upper arm kinematics and electromyograms (EMG) of eight upper extremity muscles were recorded during shoulder abduction-adduction and flexion-extension tasks in eleven participants with FSHD and 11 healthy participants. Normalized muscle activities were extracted from EMG signals. Non-negative matrix factorization was used to compute muscle synergies. Maximum muscle activities were compared using non-parametric analysis of variance. Similarities between synergies were also calculated using correlation. The Biceps Brachii was significantly more active in the FSHD group (25±2%) while Trapezius Ascendens and Serratus Anterior were less active (32±7% and 39±4%, respectively). Muscle synergy weights were altered in FSHD individuals and showed greater diversity while controls mostly used one synergy for both tasks. The decreased activity by selected scapula rotator muscles and muscle synergy weight alterations show that neuromuscular control of the scapulohumeral joint is less consistent in people with FSHD compared to healthy participants. Assessments of muscle coordination strategies can be used to evaluate motor output variability and assist in management of the disease.

This study's objective is to understand the effect of muscular weakness in persons with facioscapulohumeral dystrophy as well as the effect of a dynamic arm support on muscle coordination and activity performance, during activities of daily living. People with facioscapulohumeral dystrophy (n=12, 56.0±14.5 years) and healthy controls (n=12, 55.5±13.4 years) performed five simulated daily activity tasks, while unsupported and supported by the Gowing dynamic arm support. Surface electromyography, kinematics, and maximum force output were recorded. Outcomes were calculated for muscle coordination (muscle synergies), maximum muscle activity, movement performance indicators, and upper limb muscular weakness (maximum force output). Muscle coordination was altered and less consistent in persons with facioscapulohumeral dystrophy compared with healthy controls. The dynamic arm support alleviated muscle efforts and affected muscle coordination in both populations. While populations became more similar, the internal consistency of persons with facioscapulohumeral dystrophy remained unaffected and lower than that of healthy controls. Furthermore, the support affected movements’ performance in both groups. The maximum force outputs were lower in persons with facioscapulohumeral dystrophy than controls. Muscle coordination differences were presumably the result of individual-specific in muscle weakness and compensatory strategies for dealing with gravity compensation and movement constraints.

G.P.110 The DUX4 promoter is preferentially expressed in FSHD-affected tissues

To investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders. We collected 50 muscle biopsies (26 vastus lateralis, 24 tibialis anterior) from 14 patients with genetically confirmed FSHD and 12 healthy controls. Single muscle fibers (n = 547) were isolated for contractile measurements. Titin content and titin phosphorylation were examined in vastus lateralis muscle biopsies. Single muscle fiber specific force was intact at saturating and physiologic calcium concentrations in all FSHD biopsies, with (FSHDFAT) and without (FSHDNORMAL) fatty infiltration, compared to healthy controls. Myofilament calcium sensitivity of force is increased in single muscle fibers obtained from FSHD muscle biopsies with increased fatty infiltration, but not in FSHD muscle biopsies without fatty infiltration (pCa50: 5.77-5.80 in healthy controls, 5.74-5.83 in FSHDNORMAL, and 5.86-5.90 in FSHDFAT single muscle fibers). Cross-bridge cycling kinetics at saturating calcium concentrations and myofilament cooperativity did not differ from healthy controls. Development of single muscle fiber passive tension was changed in all FSHD vastus lateralis and in FSHDFAT tibialis anterior, resulting in increased fiber stiffness. Titin content was increased in FSHD vastus lateralis biopsies; however, titin phosphorylation did not differ from healthy controls. Muscle weakness in patients with FSHD is not caused by reduced specific force of individual muscle fibers, even in severely affected tissue with marked fatty infiltration of muscle tissue.

P.16.2 The DUX4 promoter is expressed in FSHD-affected tissues

184th ENMC international workshop: Pain and fatigue in neuromuscular disorders: 20–22 May 2011, Naarden, The Netherlands

Muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary myopathy causing progressive muscle weakness. FSHD has substantial impacts on function and health-related quality of life (HRQoL). Patient-reported outcome measures (PROs) are used to assess HRQoL, yet their suitability for FSHD remains unclear. (1) identify PROs used to assess HRQoL in adults with FSHD; (2) evaluate the evidence for their measurement properties; and (3) develop a conceptual HRQoL framework for FSHD. A systematic review was conducted in accordance with COSMIN and PRISMA-COSMIN guidelines (PROSPERO: CRD42024605345). Two-stage searches across seven databases (including MEDLINE, Embase, and CINAHL, last updated July 2025) identified PROs assessing HRQoL in FSHD and studies evaluating their measurement properties. Eligibility criteria included publicly available, multi-item self-report PROs scored using established systems. Screening, data extraction, and quality appraisal were performed in duplicate. Measurement properties were rated using COSMIN standards and graded with the COSMIN-modified GRADE approach. Item content of the PROs was examined, mapped to an existing framework, and subsequently refined with people living with FSHD to develop a novel HRQoL framework for FSHD (QUAL-FSHD). Fifty-six development papers and 40 research studies were included in the review, 37 studies reported data on psychometric properties. Sixty-six PROs/subscales were included. Most had evidence limited to content validity (i.e., development papers in non-FSHD populations) and construct validity. Only the Upper Extremity Functional Index (UEFI) had data across five measurement properties, though overall evidence quality was very low to moderate. Responsiveness was assessed in nine PROs, with five determined to be ‘sufficient’. The QUAL-FSHD framework comprises seven themes and 44 subthemes. Mapping of the PROs found 21% (n = 14) covered aspects of physical, psychological, and social functioning, with no instrument covering all subthemes. Current publicly available HRQoL PROs used in FSHD exhibit significant gaps in content coverage and psychometric evidence to support their use in the condition. The QUAL-FSHD framework provides a structured, stakeholder-informed model for evaluating HRQoL in FSHD. There is an urgent need for future research to establish content validity, psychometric performance, and acceptable respondent burden of existing PROs to ensure accurate assessment of HRQoL outcomes in FSHD. Not applicable.

The Facioscapulohumeral Muscular Dystrophy (FSHD) is an autosomal dominant neuromuscular disorder whose incidence is estimated in about one in 400,000 to one in 20,000. No effective therapeutic strategies are known to halt progression or reverse muscle weakness and atrophy. It is known that the FSHD is caused by modifications located within a D4ZA repeat array in the chromosome 4q, while recent advances have linked these modifications to the DUX4 gene. Unfortunately, the complete mechanisms responsible for the molecular pathogenesis and progressive muscle weakness still remain unknown. Although there are many studies addressing cancer databases from a machine learning perspective, there is no such precedent in the analysis of the FSHD. This study aims to fill this gap by analyzing two specific FSHD databases. A feature selection algorithm is used as the main engine to select genes promoting the highest possible classification capacity. The combination of feature selection and classification aims at obtaining simple models (in terms of very low numbers of genes) capable of good generalization, that may be associated with the disease. We show that the reported method is highly efficient in finding genes to discern between healthy cases (not affected by the FSHD) and FSHD cases, allowing the discovery of very parsimonious models that yield negligible repeated cross-validation error. These models in turn give rise to very simple decision procedures in the form of a decision tree. Current biological evidence regarding these genes shows that they are linked to skeletal muscle processes concerning specific human conditions.

ANT1 overexpression models: Some similarities with facioscapulohumeral muscular dystrophy

Mortality associated with facioscapulohumeral muscular dystrophy: A systematic literature review.

Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction

OP1-5 - Oxidative stress and dystrophy Facioscapulohumeral: Effects of vitamin C, vitamin E, zinc gluconate and selenomethionine supplementation

Facioscapulohumeral muscular dystrophy (FSHD), was one of the first diseases shown to be caused by an unstable repeat in the early 1990s along with spinal and bulbar muscular atrophy (SBMA), myotonic dystrophy (DM1), and fragile X mental retardation (FRAXA), where the latter three are caused by genetically expanding trinucleotide repeats [1]. However, FSHD differs considerably from the trinuclotide repeat diseases, as it is caused by a contraction of a macrosatellite (D4Z4 repeat, 3.3 kb/unit). Moreover, far less is understood about the pathogenic mechanism for FSHD, relative to SBMA, DM1, and FRAXA. This is not due to a shortage of experimental efforts, plausible hypotheses, or collaborative efforts towards understanding FSHD [2], [3]. The elucidation of FSHD is hampered by the size of the unstable repeat, its sequence complexity, the number of repeat units, and the presence of the repeat on Chromosomes 4 and 10, making analysis technically difficult. The difficulty is compounded further by the absence of an obvious gene, transcript, or protein in the unstable or proximal region; in fact, the D4Z4 repeats have been referred to as “junk” DNA or are thought to be a pseudogene, at best. As a result, FSHD has proved to be one of the most complex and challenging genetic diseases to even a glimpse an underlying pathogenic cause for FSHD. Several recent papers, including one in this issue of PLoS Genetics [4], have made significant advances that now permit us to expand our understanding of FSHD pathogenesis, a repeat contraction disease. FSHD presents with weakness of facial muscles, stabilizers of the scapula, or dorsiflexors of the foot. The weakness is progressive with age. Disease severity is highly variable and shows some signs of anticipation, common to other repeat-associated diseases. FSHD is autosomal dominant, characterized by a deletion of D4Z4 repeat units, located in the subtelomere of chromosome 4q35 (Figure 1). Non-affected D4Z4 alleles are polymorphic having 11–100 repeat units; individuals affected with FSHD have 10 or fewer units, but must have at least one unit to show disease, which is now known to be the most telomeric unit. D4Z4 contractions can be inherited or occur as de novo mutations. The contracted D4Z4 repeat arrays show loss of DNA methylation and reduced histone 3 lysine 9 trimethylation, consistent with a more open chromatin structure [5]. The role of the altered chromatin in FSHD pathogenesis is controversial and has been suggested to enhance expression of adjacent genes like FRG1 or ANT1 [6]. More recently, FSHD2-affected individuals that display the altered chromatin but have non-contracted D4Z4 repeats have implicated the derepression of a DUX4 transcript encoded on the D4Z4 repeat units [7], [8]. However, the mechanism through which the altered chromatin at D4Z4 repeats contributes to FSHD remains unclear. Figure 1 Simplified schematic outlining the genetic requirements for FSHD and the current model for pathogenesis.