OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA, indicating that regional biopsies can accurately measure progression in the whole muscle and providing a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design. An unanticipated finding was the strong correlations of molecular signatures in the bilateral comparisons, including markers of B-cells and other immune cell populations, suggesting that a systemic immune cell infiltration of skeletal muscle might have a role in disease progression.

A forty-four-year-old female patient known for FSHD type I, with unremarkable past ocular history, complained of progressive visual acuity deterioration during a routine ophthalmological visit. Best-corrected visual acuity (BCVA) was 1.0 decimal Snellen equivalent bilaterally. Dilated fundus examination showed evidence of retinal Coats-like disease in the left eye, while the right eye showed significant retinal vascular tortuosity. Multimodal examinations (OCT scans and FA-fluorescein angiography) revealed large areas of retinal ischemia, thus confirming a retinal vascular disorder compatible with the diagnosis of Coats-like disease. Left eye laser photocoagulation of the ischemic areas was performed to avoid neovascular complications that had not been detected during follow-up visits (12 months), and BCVA in the left eye remained stable at 1.0 decimals Snellen equivalent. Coats-like disease in a patient affected by FSHD type I should always be screened even in the absence of any prior ocular diseases. Guidelines concerning the ophthalmological management of adults affected by FSHD are lacking. Based on this case, we recommend performing a yearly complete ophthalmological checkup with dilated fundus examination and retinal imaging. Patients should, furthermore, be encouraged to seek medical attention when noticing deterioration of visual acuity or other visual symptoms in order to avoid missing potential sight-threatening ocular complications.

This review highlights ten important advances in the neuromuscular disease field that were reported in 2022. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 and 2022 reviews), DNAJB4-associated myopathy, NMNAT2-deficient hereditary axonal neuropathy, Guillain-Barré syndrome, sporadic inclusion body myositis, and amyotrophic lateral sclerosis. In addition, the review highlights a few other advances (including new insights into mechanisms of fiber maturation during muscle regeneration and fiber rebuilding following reinnervation, improved genetic testing methods for facioscapulohumeral and myotonic muscular dystrophies, and the use of SARM1 inhibitors to block Wallerian degeneration) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease.

BACKGROUND: Scapulothoracic (ST) fusion for facioscapulohumeral muscular dystrophy (FSHD) is an established treatment that corrects scapular instability, although it has high reported complication rates. The purpose of our study was to characterize the outcomes of ST fusion for FSHD in a large patient cohort and compare the outcomes based on bone graft type and fixation technique. Our hypothesis was that union rates would not differ by bone graft type during ST fusion.
METHODS: A retrospective chart review was undertaken to identify patients who underwent ST fusion at multiple institutions performed by a single surgeon between 2013 and 2019 with minimum 2-year follow-up. Patient demographic characteristics, surgical technique, time to union, complications, and clinical outcomes including patient-reported outcome measures were recorded. Univariate and multivariate statistical analyses including regression analyses were performed to compare preoperative and postoperative outcomes.
RESULTS: A total of 50 patients with 54 ST fusions (bilateral in 4 patients) and an average follow-up period of 5.8 years (standard deviation, 1.6 years) were included for analysis. Active forward elevation (77° vs. 124°, P < .00001) and abduction (60° vs. 90°, P < .00001) both improved significantly after fusion. Average internal rotation after fusion was at spinal level L3-L4. The visual analog scale pain score (2.6 vs. 1.2, P < .00001), Subjective Shoulder Value score (33 vs. 76, P < .00001), and American Shoulder and Elbow Surgeons (ASES) score (41.8 vs. 76.1, P < .00001) all improved significantly postoperatively. Of the shoulders, 50% (27 of 54) received treatment with cerclage wires and 50% (27 of 54) received treatment with Luque wires. Femoral head allograft was used in 53.7% of shoulders (29 of 54), whereas iliac crest autograft was used in 46.3% (25 of 54). Average radiographic time to healing was 11.1 weeks (standard deviation, 3.2 weeks), with no incidence of nonunion, and did not significantly differ by bone graft type (P = .26) or technique (P = .20). The complication rate was 24.1%, including seroma (n = 3), superficial infection (n = 2), transient neurologic injury (n = 2), hemothorax (n = 1), rib fracture (n = 1), pneumothorax (n = 1), and shortness of breath (n = 1), although none requiring reoperation. There was no significant difference in the rate of postoperative complications when compared by surgical technique (P = .81) and bone graft type (P = .93). There were no independently predictive factors influencing the rate of postoperative complications by multivariate regression. Regression analysis showed that the postoperative ASES score was independently associated with the preoperative ASES score (P < .0001), use of iliac crest autograft (P < .011), and presence of complications (P < .043).
CONCLUSIONS: Patients receiving ST fusion for FSHD demonstrate globally improved active motion and patient-reported outcome measures. Fusion construct or type of bone graft does not affect time to union or complication rates. Surgeons should be aware of a relatively high complication rate in the early postoperative period.

Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary disorder which typically results in scapular winging due to wasting of the periscapular muscles affected by this condition. Scapulothoracic arthrodesis (STA) is the current surgical treatment for FSHD patients with severe winging and preserved deltoid muscle. There are several different techniques in the literature such as multifilament cables alone and cable or cerclage wires combined with single or multiple plates. We prefer cables without plates as it provides independent strong fixation points and strongly recommend utilization of autograft. The functional results of studies report that regardless of the technique used, shoulder elevation and thus quality of life is improved, as shown with outcome scores. There are several complications associated with STA. Pulmonary complications are common and usually resolve spontaneously. Meticulous surgical technique and effective postoperative analgesia may reduce the incidence. Scapular complications which are associated with the fixation may be encountered in the early or late period, which are related to the learning curve of the surgeon. In conclusion, STA is a reliable solution to a major problem in FSHD patients that helps them maintain their activities of daily living until a cure for the disease is found. A successful result is strongly dependent on patient selection, and a multidisciplinary team of neurologists, geneticists and orthopaedic surgeons is required to achieve good results.

The aim of this report is to describe the management of a severe spinal deformity in an adolescent with facioscapulohumeral dystrophy (FSHD) and review the available literature on the topic.
A 14-year-old patient with a genetically confirmed diagnosis of FSHD was evaluated for right thoracolumbar scoliosis (TL) and severe lumbar hyperlordosis. Spinal radiographs showed a right-sided curve of 32° and in the sagittal plane a lordotic curve T10-S1 -143°, TL junction -51.6°, LL -115°, pelvic incidence (PI) 25.5°, pelvic tilt 63.3°, PI-LL mismatch -90°, and a sagittal imbalance of -146 mm. An MRI scan evidenced atrophy of the paraspinal muscles. An instrumental gait analysis revealed significant pelvic anteversion associated with hip flexion and mild equinus. During follow-up, the patient developed a progressive inability to walk and difficulty sitting along with respiratory compromise and pain.
At the age of 16 years, a posterior T2-iliac spinal fusion was performed using pedicle screws and four iliac anchors, with a 4-rod system placed at the lumbopelvic level. Significant correction of the hyperlordosis, the PI-LL mismatch, and sagittal imbalance was achieved, and the patient improved her sitting capacity, quality of life (QoL) and self-esteem and reported a decreased perception of disability at 2-year follow-up.
This is the first published case of spinal deformity secondary to FSHD to use gait analysis to supplement the decision of optimal timing for surgery, and the second published case of spine surgery in a pediatric patient. Although spinal fusion surgery is controversial in ambulatory FSHD patients with extensive deformity, when ambulation is impaired, surgery improves function, prevents progression, and restores sagittal balance, increasing patient\'s QoL.

BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is a progressive muscle dystrophy disorder leading to significant disability. Currently, FSHD symptom severity is assessed by clinical assessments such as the FSHD clinical score and the Timed Up-and-Go test. These assessments are limited in their ability to capture changes continuously and the full impact of the disease on patients\' quality of life. Real-world data related to physical activity, sleep, and social behavior could potentially provide additional insight into the impact of the disease and might be useful in assessing treatment effects on aspects that are important contributors to the functioning and well-being of patients with FSHD.
OBJECTIVE: This study investigated the feasibility of using smartphones and wearables to capture symptoms related to FSHD based on a continuous collection of multiple features, such as the number of steps, sleep, and app use. We also identified features that can be used to differentiate between patients with FSHD and non-FSHD controls.
METHODS: In this exploratory noninterventional study, 58 participants (n=38, 66%, patients with FSHD and n=20, 34%, non-FSHD controls) were monitored using a smartphone monitoring app for 6 weeks. On the first and last day of the study period, clinicians assessed the participants\' FSHD clinical score and Timed Up-and-Go test time. Participants installed the app on their Android smartphones, were given a smartwatch, and were instructed to measure their weight and blood pressure on a weekly basis using a scale and blood pressure monitor. The user experience and perceived burden of the app on participants\' smartphones were assessed at 6 weeks using a questionnaire. With the data collected, we sought to identify the behavioral features that were most salient in distinguishing the 2 groups (patients with FSHD and non-FSHD controls) and the optimal time window to perform the classification.
RESULTS: Overall, the participants stated that the app was well tolerated, but 67% (39/58) noticed a difference in battery life using all 6 weeks of data, we classified patients with FSHD and non-FSHD controls with 93% accuracy, 100% sensitivity, and 80% specificity. We found that the optimal time window for the classification is the first day of data collection and the first week of data collection, which yielded an accuracy, sensitivity, and specificity of 95.8%, 100%, and 94.4%, respectively. Features relating to smartphone acceleration, app use, location, physical activity, sleep, and call behavior were the most salient features for the classification.
CONCLUSIONS: Remotely monitored data collection allowed for the collection of daily activity data in patients with FSHD and non-FSHD controls for 6 weeks. We demonstrated the initial ability to detect differences in features in patients with FSHD and non-FSHD controls using smartphones and wearables, mainly based on data related to physical and social activity.
BACKGROUND: ClinicalTrials.gov NCT04999735; https://www.clinicaltrials.gov/ct2/show/NCT04999735.

The full spectrum of the clinical phenotype of facioscapulohumeral muscular dystrophy (FSHD), beyond skeletal muscle weakness, remains poorly characterized. In this study, we describe systemic manifestations and symptom burden in a large series of FSHD patients.
We performed a retrospective chart review of FSHD patients seen at our institution between 2000 and 2017. We reviewed patients\' responses to a comprehensive review of symptoms and the results of diagnostic testing for sensorineural hearing loss, cardiac disease, dysphagia, ocular abnormalities, and respiratory insufficiency. We assessed the association between disease manifestations and age of onset, genetic profile, and disease duration.
We identified 87 patients with FSHD. The most common reported symptoms included pain (71%), difficulty sleeping (41%), headaches (27%), and altered mood (24%). When tested, 7 of 16 (44%) patients had sensorineural hearing loss, 20 of 60 (33%) had cardiac arrhythmias or conduction defects, 17 of 45 (38%) had echocardiogram abnormalities, 12 of 25 (48%) had reduced forced vital capacity, and 4 of 10 (40%) had oropharyngeal dysphagia. However, patients with these abnormalities represented 8%, 23%, 20%, 14%, and 5% of total number of patients, respectively, as uniform screening was lacking. Ocular pathology attributable to FSHD was not detected.
FSHD demonstrates a broad clinical phenotype. Increased vigilance among neurologists to screen for systemic manifestations of the disease is warranted. More uniform screening and future population-based studies are needed to compare findings in FSHD patients with the general population.

BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is a late-onset autosomal dominant form of muscular dystrophy involving specific groups of muscles with variable weakness that precedes inflammatory response, fat infiltration, and muscle atrophy. As there is currently no cure for this disease, understanding and modelling the typical muscle weakness in FSHD remains a major milestone towards deciphering the disease pathogenesis as it will pave the way to therapeutic strategies aimed at correcting the functional muscular defect in patients.
METHODS: To gain further insights into the specificity of the muscle alteration in this disease, we derived induced pluripotent stem cells from patients affected with Types 1 and 2 FSHD but also from patients affected with Bosma arhinia and microphthalmia. We differentiated these cells into contractile innervated muscle fibres and analysed their transcriptome by RNA Seq in comparison with cells derived from healthy donors. To uncover biological pathways altered in the disease, we applied MOGAMUN, a multi-objective genetic algorithm that integrates multiplex complex networks of biological interactions (protein-protein interactions, co-expression, and biological pathways) and RNA Seq expression data to identify active modules.
RESULTS: We identified 132 differentially expressed genes that are specific to FSHD cells (false discovery rate < 0.05). In FSHD, the vast majority of active modules retrieved with MOGAMUN converges towards a decreased expression of genes encoding proteins involved in sarcomere organization (P value 2.63e-12 ), actin cytoskeleton (P value 9.4e-5 ), myofibril (P value 2.19e-12 ), actin-myosin sliding, and calcium handling (with P values ranging from 7.9e-35 to 7.9e-21 ). Combined with in vivo validations and functional investigations, our data emphasize a reduction in fibre contraction (P value < 0.0001) indicating that the muscle weakness that is typical of FSHD clinical spectrum might be associated with dysfunction of calcium release (P value < 0.0001), actin-myosin interactions, motor activity, mechano-transduction, and dysfunctional sarcomere contractility.
CONCLUSIONS: Identification of biomarkers of FSHD muscle remain critical for understanding the process leading to the pathology but also for the definition of readouts to be used for drug design, outcome measures, and monitoring of therapies. The different pathways identified through a system biology approach have been largely overlooked in the disease. Overall, our work opens new perspectives in the definition of biomarkers able to define the muscle alteration but also in the development of novel strategies to improve muscle function as it provides functional parameters for active molecule screening.