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Quality of life (QoL) in children with facioscapulohumeral dystrophy (FSHD) seems plausible decreased. Little is known about factors influencing QoL in children with FSHD. Our objective is to explore factors contributing to the QoL of children, adolescents, and young adults with FSHD, to describe how they experience life with FSHD, and to report their support needs. We performed a mixed-method study with individual age-appropriate semi-structured interviews assessing QoL in children, adolescents, and young adults with FSHD and their parents. To characterize the sample, quantitative data on QoL, pain, fatigue, and participation were collected. Interview data was analyzed using a thematic analysis. Fourteen patients participated (age between 9 and 26 years old, eight males and six females). The degree of FSHD severity, as indicated by the FSHD-score, did not correlate with QoL. Older children had a lower QoL than younger children. Children and adolescents strived for normality regardless of physical discomfort. Phenotypical features of FSHD led to insecurity aggravated by hurtful comments of others. The unpredictability of disease progression and its implications for career and parenthood choices led to a generalized feeling of uncertainty about the future. Support was found within family and friends. Participants expressed a need for peer support and psychological support as well as recommending it to others. Quality of life in childhood FSHD is diminished caused by their physical limitations, altered appearance, fear of social rejection, and uncertainty of the disease progression in the future. A fear of social rejection most likely contributes to striving for normality regardless of physical discomfort. Support should be focused on acceptance and coping with hurtful comments. It should preferably be individualized, easily accessible and not offered as therapy but rather as tutoring for children. • Quality of life in children with facioscapulohumeral dystrophy is decreased. • Facioscapulohumeral dystrophy affects different aspects of children's life. • Children strive for normality regardless of physical discomfort. • The uncertainty about the disease progression is worrying for adolescents. • Support should focus on acceptance and not framed as 'therapy'. [ABSTRACT FROM AUTHOR]

This study aimed to establish the relative incidence of etiologies causing serratus anterior (SA) dysfunction in patients with proven abnormality on needle electromyography. This was a retrospective review of patients with scapular winging secondary to SA dysfunction. Each patient underwent a detailed clinical, radiological, and neurophysiological assessment to arrive at the precise etiological diagnosis. Patients with atypical clinical features were referred for a neurologist's assessment. Hematological and genetic testing were requested at the discretion of the neurologist. A scapular winging severity score based on clinical signs was devised to aid clinical grading. Between 2014 and 2020, a consecutive series of 108 patients with suspected SA dysfunction were assessed, of whom 96 met the inclusion criteria. There were 34 females and 62 males, with a mean age of 38 years (range, 15-77 years). Winging affected the right scapulae in 69 patients, the left scapulae in 17 patients, and was bilateral in 10 patients. This was caused by a myopathic disorder in 12 (12%) patients. Eighty-four (88%) patients had a long thoracic nerve lesion, caused by cervical pathology (2), iatrogenic injury (2), trauma (33), and neuralgic amyotrophy (NA) (47). Among those with NA, winging resolved spontaneously within 3 years of onset in 22 patients (mean duration, 16 months; range, 3-36 months). No patients recovered fully if their duration of winging lasted longer than 3 years. Patients with palsy secondary to NA tended to have a worse severity of winging than those due to a traumatic cause (P =.04). NA accounted for approximately half of the patients with SA dysfunction; therefore, it is essential to also consider the differentials of myopathy, trauma, iatrogenic injury, and spinal pathology. We recommend the judicious employment of ancillary tests and a low threshold of referral to a neurologist, in order to arrive at the exact diagnosis to accurately guide patient treatment. [ABSTRACT FROM AUTHOR]

Highlights • Bariatric surgery is a treatment option for obesity when other tools have failed, also in patients with FSHD and DM1. • We obtained insight into the outcome, effects and risks from a patients perspective. • This improves counseling of patients with FSHD and DM1 who consider bariatric surgery. Abstract Overweight and obesity are common in patients with facioscapulohumeral dystrophy (FSHD) and myotonic dystrophy type 1 (DM1). Lifestyle change is often challenging for patients with neuromuscular diseases, especially to increase physical activity. When lifestyle changes have not been effective, bariatric surgery is a treatment option. However, very little is known about the benefits and risks in patients with neuromuscular disorders. This study therefore aims to obtain insight into the patients' perspectives and experiences, the outcome, effects and risks of bariatric surgery in these disorders. We performed a qualitative study, consisting of 14 in-depth interviews with six patients (three FSHD and three DM1; five women, one man; aged range 31–47 years), four relatives, three bariatric surgeons and one general practitioner. The study used a qualitative descriptive method. Four themes were formulated: (1) overweight as burden; (2) bariatric surgery as last option; (3) not your standard patient; and (4) a different life, a different me. This study shows that bariatric surgery has beneficial physical and mental effects for most patients with FSHD and DM1, and does not influence the muscular disease course. Bariatric surgery is feasible in patients with FSHD and DM1, but specific precautions and a suitable follow-up including tailored dietary and training advices are required. [ABSTRACT FROM AUTHOR]

Abstract Aim To assess the long-term natural course of early-onset facioscapulohumeral dystrophy (FSHD), which is important for patient management and trial-readiness, and is currently lacking. Methods We had the unique opportunity to evaluate 10 patients with early-onset FSHD after 22 years follow-up. Patients underwent a semi-structured interview, physical examination and additional genotyping. Results Nine initial study participants (median age 37 years) were included, one patient died shortly after first publication. At first examination, one patient was wheelchair dependent, one patient walked aided, and eight patients walked unaided. After 22 years, four patients were wheelchair dependent, three walked aided, and two walked unaided. Systemic features, including hearing loss (56%), intellectual disability (44%), and a decreased respiratory function (56%), were frequent. Patients participated socially and economically with most patients living in a regular house (n = 6) and/or having a paid job (n = 4). Discussion Patients with early-onset FSHD generally had a severe phenotype compared to classical onset FSHD. However, after 22 years of follow up they showed a wide variation in severity and, despite these physical limitations, participated socially and economically. These observations are important for patient management and should be taken into account in clinical trials. Highlights • First report on long-term follow-up of early-onset facioscapulohumeral muscular dystrophy. • Patients showed severe muscle weakness and frequent systemic features. • However, the phenotype was heterogenic including mildly affected patients as well. • Most patients remained independent with help and participated socially and economically. [ABSTRACT FROM AUTHOR]

Infantile or early onset is estimated to occur in around 10% of all facioscapulohumeral dystrophy (FSHD) patients. Although small series of early onset FSHD patients have been reported, comprehensive data on the clinical phenotype is missing. We performed a systematic literature search on the clinical features of early onset FSHD comprising a total of 43 articles with individual data on 227 patients. Additional data from four cohorts was provided by the authors. Mean age at reporting was 18.8 years, and 40% of patients were wheelchair-dependent at that age. Half of the patients had systemic features, including hearing loss (40%), retinal abnormalities (37%) and developmental delay (8%). We found an inverse correlation between repeat size and disease severity, similar to adult-onset FSHD. De novo FSHD1 mutations were more prevalent than in adult-onset FSHD. Compared to adult FSHD, our findings indicate that early onset FSHD is overall characterized by a more severe muscle phenotype and a higher prevalence of systemic features. However, similar as in adults, a significant clinical heterogeneity was observed. Based on this, we consider early onset FSHD to be on the severe end of the FSHD disease spectrum. We found natural history studies and treatment studies to be very scarce in early onset FSHD, therefore longitudinal studies are needed to improve prognostication, clinical management and trial-readiness. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral dystrophy (FSHD) is one of the three most common muscular dystrophies in the Western world, however, its etiology remains only partially understood. Here, we provide evidence of constitutive DNA damage in in vitro cultured myoblasts isolated from FSHD patients and demonstrate oxidative DNA damage implication in the differentiation of these cells into phenotypically-aberrant myotubes. Double homeobox 4 (DUX4), the major actor in FSHD pathology induced DNA damage accumulation when overexpressed in normal human myoblasts, and RNAi-mediated DUX4 inhibition reduced the level of DNA damage in FSHD myoblasts. Addition of tempol, a powerful antioxidant, to the culture medium of proliferating DUX4 -transfected myoblasts and FSHD myoblasts reduced the level of DNA damage, suggesting that DNA alterations are mainly due to oxidative stress. Antioxidant treatment during the myogenic differentiation of FSHD myoblasts significantly reduced morphological defects in myotube formation. We propose that the induction of DNA damage is a novel function of the DUX4 protein affecting myogenic differentiation of FSHD myoblasts. [ABSTRACT FROM AUTHOR]

Scapular mobility has a central role in maintaining normal upper limb function. Scapular winging is characterized by a failure in the dynamic stabilization of the scapula against the thoracic wall resulting in a condition in which the medial border of the scapula is prominent. The following case describes a patient who was referred to physiotherapy due to abnormal scapular protrusion. The main findings of the physical examination showed weakness of the scapular stabilizers more prominent on the right side than of the left. Additionally, the physical examination demonstrated weakness of the abdominal muscles, hip adductors, and ankle dorsi-flexors, as well as some facial muscles. The electromyography results were inconclusive. Further examination led to clinical suspicion of Facioscapulohumeral Dystrophy (FSHD) as a diagnosis, which was confirmed by genetic testing. Facioscapulohumeral Dystrophy is characterized by symptoms related to motor function and in most cases becomes evident in patients in their 20s and 30s. The disease signs and symptoms are often identified in a clinical setting. Currently, there are no reports describing an effective treatment for the disease. However, physiotherapy, moderate physical exercise, counselling, and use of suitable aids and orthoses may help improve functionality and mobility. This case report aims to increase the awareness of musculoskeletal physiotherapists to this unique dystrophy, when encountering complex presentations with scapular winging. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral dystrophy (FSHD) is a unique and complex genetic disease that is not entirely solved. Recent advances in the field have led to a consensus genetic premise for the disorder, enabling researchers to now pursue the design of preclinical models. In this review we explore all available FSHD models (DUX4-dependent and -independent) for their utility in therapeutic discovery and potential to yield novel disease insights. Owing to the complex nature of FSHD, there is currently no single model that accurately recapitulates the genetic and pathophysiological spectrum of the disorder. Existing models emphasize only specific aspects of the disease, highlighting the need for more collaborative research and novel paradigms to advance the translational research space of FSHD. [ABSTRACT FROM AUTHOR]

Background: Scapulothoracic fusion (STF) may be an option to alleviate pain and restore function. The purpose of this study is to report the clinical outcome of patients who underwent STF for the treatment of painful scapular winging. Materials and methods: From 1999 through 2008, 10 patients (12 shoulders) underwent an STF for painful winging of the scapula. The mean follow-up period was 41 months (range, 8-72 months). Indications for STF included winging in association with excessive medial and/or lateral clavicular resection and facioscapulohumeral dystrophy, as well as scapular winging related to combined long thoracic and spinal accessory nerve palsy. A retrospective review was performed to evaluate the subjective shoulder value, visual analog scale score, range of motion, unions, and complications. Results: There was a statistically significant improvement in the subjective shoulder value, visual analog scale score, range of motion, and satisfaction postoperatively. The overall complication rate was 50% (6 of 12). There were 2 persistent nonunions (2 of 12, 17%), and 50% (6 of 12) of all fusions required subsequent hardware removal because of discomfort. Complications included pleural effusion (3 of 12, 25%), hemopneumothorax (1 of 12, 8%) pulmonary embolus (1 of 12, 8%), and infection (1 of 12, 8%). With the exception of the revision nonunion, all complications resolved with no negative sequelae. Conclusion: STF results in improved function and pain relief. STF is associated with a high short-term complication rate with limited long-term sequelae. [Copyright &y& Elsevier]

Abstract: Scapulothoracic fusion can, in appropriately selected cases, achieve substantial pain relief and functional improvement for the patient. It can be indicated in patients with severe scapular winging who have failed nonoperative rehabilitation measures and dynamic muscle transfers. In 1921, the first true scapulothoracic arthrodesis was performed using a portion of the fourth rib without internal fixation. Since then, a multitude of different techniques have been tried to secure the scapula against the thorax. Initially techniques introduced metal wires, before progression onto the use of wires with a plate to distribute the forces and, more recently, a plate with screw fixation to the ribs. Various complications have been reported, including metalwork failure, adhesive capsulitis, nonunion, pneumothorax, pleural effusion, thoracic outlet syndrome, pneumonia, scapula fracture and deep venous thrombosis. Scapulothoracic fusion can relieve shoulder pain, allow for smooth functional abduction and flexion of the upper extremity and can improve the appearance of the neck and shoulder in patients who have symptomatic scapular winging. The procedure is associated with a significant complication rate, although many of the potential complications resolve without an extended period of morbidity for the patient. [Copyright &y& Elsevier]

Abstract: We report the first case of a heterozygous T78M mutation in the caveolin-3 gene (CAV3) associated with rippling muscle disease and proximal myopathy. The patient displayed also bilateral winged scapula with limited abduction of upper arms and marked asymmetric atrophy of leg muscles shown by magnetic resonance imaging. Immunohistochemistry on the patient’s muscle biopsy demonstrated a reduction of caveolin-3 staining, compatible with the diagnosis of caveolinopathy. Interestingly, consistent with the possible diagnosis of FSHD, the patient carried a 35kb D4Z4 allele on chromosome 4q35. We discuss the hypothesis that the two genetic mutations may exert a synergistic effect in determining the phenotype observed in this patient. [Copyright &y& Elsevier]

Abstract: Only sparse information is available concerning the relationship between pregnancy and hereditary neuromuscular disorders. This review deals with several issues like the effects of such conditions on female fertility (myotonic dystrophy type 1 and mitochondrial disorders), on the risk to the fetus (myotonic dystrophy type 1 and Charcot-Marie-Tooth disease), on the ability to carry pregnancy and its complications (markedly increased preterm labor in myotonic dystrophies and spinal muscular atrophy), on the labor and its possible need for interventions (myotonic dystrophy type 1, facioscapulohumeral dystrophy and Charcot-Marie-Tooth disease). It also discusses the question of pregnancy effects on the course of the inherited neuromuscular disorders (myotonic dystrophies, spinal muscular atrophy, facioscapulohumeral dystrophy, Charcot-Marie-Tooth disease, congenital myopathy and limb-girdle muscular dystrophy). The aim of this critical review is to point at pregnancy-related problems that need further research. [Copyright &y& Elsevier]

Abstract: Facioscapulohumeral dystrophy (FSHD), is a muscular dystrophy that classically affects the shoulder girdle and facial muscles. It should be considered in the differential diagnosis of patients presenting with limb girdle weakness. Progression is usually slow, and the condition is rarely fatal. Treatment is mostly supportive, although a number of patients can be helped with scapulo-thoracic fusion. This paper summarises the current understanding of this form of muscular dystrophy. [Copyright &y& Elsevier]

Abstract: Despite the discovery of the deletion on the long arm of the chromosome 4 specific for facioscapulohumeral muscular dystrophy (FSHD), the identity of the gene responsible for the disease still remains a mystery. In this review we focus on two genes, DUX4 and DUX4c, encoded by the D4Z4 repeats present in the 4q35 locus, which is affected in the disease. [Copyright &y& Elsevier]

The DUX4 transcription factor is briefly expressed in the early cleavage-stage embryo, where it induces an early wave of zygotic gene transcription, whereas its mis-expression in skeletal muscle causes the muscular dystrophy facioscapulohumeral dystrophy (FSHD). Here, we show that DUX4 induces the expression of the histone variants H3.X and H3.Y. We have used a myoblast cell line with doxycycline-inducible DUX4 to show that these histone variants are incorporated throughout the body of DUX4-induced genes. Following a brief pulse of DUX4, these histones contribute to greater perdurance and to enhanced re-activation of DUX4 target gene expression. These findings provide a model for H3.X/Y as a chromatin mechanism that facilitates the expression of DUX4 target genes subsequent to a brief pulse of DUX4 expression. • The cleavage-stage transcription factor DUX4 induces histone variants H3.X and H3.Y • H3.X/Y incorporate into genes transcriptionally induced by DUX4 • H3.X/Y incorporation results in enhanced re-activation of DUX4-regulated genes • H3.X/Y are necessary to amplify the DUX4 network in FSHD muscle cells Resnick et al. show that the DUX4-induced histone variants, H3.X and H3.Y, incorporate into the chromatin of DUX4-induced genes, making them more sensitive to subsequent expression. This suggests a mechanism for how the brief expression of DUX4 can establish a memory of its transcriptional network. [ABSTRACT FROM AUTHOR]

Background: Scapulothoracic arthrodesis is a recognized treatment for impaired shoulder function in patients with facioscapulohumeral dystrophy (FSHD) and is traditionally performed with autograft. The purpose of the study was to report our experience with scapulothoracic arthrodesis in patients with FSHD using allograft, rather than autograft, with particular respect to the effect of fusion on preoperative and postoperative Disabilities of the Arm, Shoulder and Hand (DASH) scores; forced vital capacity (FVC); and complications. Materials and methods: The early results of 14 consecutive scapulothoracic arthrodeses in FSHD patients with cerclage wires, plates, and allograft (fresh-frozen femoral heads) are reported. DASH scores were recorded preoperatively and 6 months postoperatively. Preoperative and 6-month FVCs were compared. The surgical technique is described. Results: Eleven patients underwent 14 fusions. The mean follow-up period was 29 months (range, 6-50 months). Forward flexion improved from 70° to 115° (P = .001) and abduction from 68° to 109° (P = .007). The DASH score improved from 48 points to 34 points (P = .005). FVC decreased from 98% to 92% of predicted (P = .021), although this was not clinically significant. One patient required revision for nonunion, and metalwork was removed in 5 scapulae. A postoperative chest infection developed in 1 patient and a pleural effusion in another. One brachial plexus palsy occurred, which had almost completely resolved by 27 months postoperatively. Conclusion: Scapulothoracic arthrodesis can be performed successfully with allograft. The nonunion and complication rates are similar to those in the existing literature. A small decrease in FVC does occur but not to a clinically significant level. [Copyright &y& Elsevier]