Search

Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4–25 years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography‐mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age‐associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P < 0.0001 and r = 0.764, P < 0.0001 respectively). The age‐associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non‐ambulant subjects, suggesting a threshold of 18–22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D3Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. Key points: The non‐invasive D3creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non‐ambulant patients.The difference in %MM between ambulant and non‐ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM.The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability. [ABSTRACT FROM AUTHOR]

Dystrophin, a protein crucial for various brain regions governing higher-order functions like learning and memory is notably absent in individuals with Duchenne muscular dystrophy (DMD). This absence of dystrophin in the brain is believed to underlie cognitive challenges in DMD. Cognitive and motor challenges observed in DMD could potentially hinder the execution of dual tasks. Is there a significant correlation between dual-task performance, functional mobility, and balance in children with DMD? The study included 28 participants (14 DMD, 14 typical development). Timed Up and Go (TUG) test results were recorded for single and dual-task conditions (motor-motor, cognitive-motor). Functional level was assessed using Motor Function Measurement-32 (MFM-32), Brooke Upper Extremity Scale, and Vignos Scale. Balance was evaluated using Balance Master System and Pediatric Functional Reach Test (PFRT). Significant differences in TUG test scores across conditions were observed in both DMD and typical development groups (p < 0.05). Children with DMD exhibited longer completion times compared to typical development children (p < 0.05). Among children with DMD, there was a significant correlation between TUG scores in different task conditions and balance assessment (p < 0.05, r = 0.571 to −0.819). Lower MFM-32 scores in DMD children were correlated with worse TUG performance across conditions (p < 0.05, r = 0.586 to −0.868). This study sheds light on the multifaceted nature of dual-tasking challenges in individuals with DMD, thereby contributing to a deeper understanding of the implications for rehabilitation strategies. [Display omitted] • Dual-task conditions deteriorated functional mobility of children with DMD and typical development. • The cognitive-motor dual-task has the greatest impact on functional mobility. • DMD population shows lower single- and dual-task performance than healthy children. • In DMD, better balance associated with improved single- and dual-task performance. • In DMD, high functional level correlated with improved single- and dual-task performance. [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of this study was to evaluate longitudinal changes using both upper limb muscle Magnetic Resonance Imaging (MRI) at shoulder, arm and forearm levels and Performance of upper limb (PUL) in ambulant and non-ambulant Duchenne Muscular Dystrophy (DMD) patients. We also wished to define whether baseline muscle MRI could help to predict functional changes after one year. Materials and Methods: Twenty-seven patients had both baseline and 12month muscle MRI and PUL assessments one year later. Results: Ten were ambulant (age range 5–16 years), and 17 non ambulant (age range 10–30 years). Increased abnormalities equal or more than 1.5 point on muscle MRI at follow up were found on all domains: at shoulder level 12/27 patients (44%), at arm level 4/27 (15%) and at forearm level 6/27 (22%). Lower follow up PUL score were found in 8/27 patients (30%) at shoulder level, in 9/27 patients (33%) at mid-level whereas no functional changes were found at distal level. There was no constant association between baseline MRI scores and follow up PUL scores at arm and forearm levels but at shoulder level patients with moderate impairment on the baseline MRI scores between 16 and 34 had the highest risk of decreased function on PUL over a year. Conclusions: Our results confirmed that the integrated use of functional scales and imaging can help to monitor functional and MRI changes over time. [ABSTRACT FROM AUTHOR]

There are an increasing number of young people with a range of life-limiting impairments in our schools, colleges, universities and communities. One of these impairments is Duchenne Muscular Dystrophy (DMD), a rare, life-limiting genetic muscle-wasting impairment that affects predominantly males. Twenty years ago, most people with DMD did not live past the age of twenty years, but now due to a range of treatments they are living longer. However, education and social care services are often yet to catch up with this improved prognosis. The aim of this paper is to compare the findings from structured conversations with members of the DMD community in Denmark and England. Historically, adults in Denmark have reported a good quality of life with an optimal health care programme and generous social care, whereas adults with DMD in England have reported poor transition to adulthood planning leading to social isolation as an adult. Findings identified three key themes: the existence of normative goals; expertise from lived experience, and the meaning of independence for someone with a complex impairment. These themes are further discussed through the lens of 'post-human thinking', and implications for practice are explored. [ABSTRACT FROM AUTHOR]

Introduction. Bethlem myopathy is a rare subtype of congenital muscular dystrophy characterized by progressive muscle weakness and joint contractures. It is a milder phenotype of the spectrum of collagen VI-related myopathies, which are caused by mutations in genes encoding collagen VI proteins, namely COL6A1, COL6A2, or COL6A3. Clinical manifestation may begin at any time from the prenatal period to late adulthood, presenting a range of symptoms from mild muscle weakness to severe disability impacting the individual's mobility and quality of life. Case description. A 13-year-old patient presented with progressive weakness affecting both arms and legs, accompanied by an inability to stand flat-footed, walk on heels, squat and rise, and experiencing calf pain after walking longer distances. Additionally, the patient struggled with lifting and carrying various objects. Since the age of 2, an abnormal gait characterized by toe walking had been observed. At 11 years old, the patient underwent Achilles tendon surgery. Physical examination revealed scapular winging, elbow contractures, muscle atrophy in the arms and legs, and follicular hyperkeratosis in the humeral and thigh regions. Elevated levels of creatine kinase were noted, along with myopathic changes evident on electroneuromyography. At 15 years old, muscle biopsy demonstrated myopathic changes without dystrophinopathy-related immunohistochemical alterations. At the age of 20, next generation sequencing analysis revealed a heterozygous variant c.1053+1G>A; p.(?) of COL6A2 gene (NM_001849.4) which is reported as pathogenic. The patient's mother, her mother, brother, and niece reported similar symptoms. Segregation analysis in affected family members revealed the same variant of COL6A2 gene. Conclusions. We present a rare case of familial Bethlem myopathy with symptoms evident from early childhood. Understanding the clinical presentation and progression of Bethlem myopathy in children is crucial for early detection, effective management, and genetic counseling. We highlight the importance of a multidisciplinary approach involving neurologists, orthopedist, geneticists, and rehabilitation specialists in providing care for patients with Bethlem myopathy, particularly in pediatric cases where early intervention can significantly impact quality of life. [ABSTRACT FROM AUTHOR]

Background: Patients with Duchenne muscular dystrophy (DMD) often develop scoliosis that progresses rapidly after loss of ambulation. Management of scoliosis is crucial because it affects both life expectancy and quality of life of patients with DMD. Spinal orthosis attempts to prevent or delay scoliosis using spinal support at three points of the controlling mechanism; the curve should be flattened by the pressure. Therefore, it is assumed that spine flexibility could be a significant influencing factor for the effectiveness of braces. Hence, we attempted to investigate the flexibility of scoliosis in non-ambulant patients with DMD.Methods: We reviewed the medical records of 273 boys who were genetically identified as having DMD, and finally, 50 boys with serial records of radiographs after loss of ambulation were finally enrolled. And among them, only 31 patients developed scoliosis. Spine radiographs in sitting and supine positions were also reviewed to obtain Cobb angle, curve flexibility, and pelvic obliquity. Flexibilities (%) were calculated by the difference in angles between the sitting and supine positions divided by the angle at the sitting position, multiplied by 100.Results: Among 31 boys who had scoliosis, all but 2 boys with curves went through a sequential course of 1) no scoliosis, 2) nonstructural scoliosis, when scoliosis was only measurable in the sitting position, and 3) structural scoliosis, when scoliosis was also detectable in the supine position. Flexibility decreased each year after detection of scoliosis in those who developed scoliosis the first year, from 75.5 ± 5.0% to 57.1 ± 10.5% and to 49.1 ± 10.0% (mean ± standard deviation). Spinal flexibility was significantly correlated with curve magnitude of scoliosis in both sitting and supine position (p < 0.05, respectively).Conclusions: There is a period of fully reducible curve in DMD patients at the initial stage of scoliosis. Afterward, as spinal curve progresses, flexibility decreases over time. To detect the scoliosis when the curve is fully reducible, scoliosis curve in DMD patients should be evaluated dynamically, including radiographs of at least in two different positions. [ABSTRACT FROM AUTHOR]

Uncertainty is a challenging aspect of caring for children with Duchenne/Becker muscular dystrophies (DBMD). Although uncertainty is often perceived as a state to be avoided, hope may influence caregivers' perceptions of uncertainty as opportunity. The goal of this cross‐sectional quantitative study was to pilot a novel measure of state‐based hope, and test relationships among uncertainty, hope, spirituality, and coping efficacy in mothers of children with DBMD. Mothers (n = 202) were recruited through DuchenneConnect, Parent Project Muscular Dystrophy, and Cincinnati's Children Hospital. A one‐component solution for the novel Parent Hope Scale explained 44.3% of the variance, and the measure showed high internal consistency. Higher hope (P < 0.001), further disease progression (P = 0.042), and older mother's age (P = 0.001) were significantly associated with lower perceptions of uncertainty. Mothers reporting less hope (P < 0.001), higher perceptions of uncertainty (P < 0.001), and less spirituality (P = 0.001) reported lower coping efficacy. As such, hope appears to be a key variable in shaping uncertainty appraisals and facilitating coping efficacy. While further research is needed, counseling aimed at bolstering hope, particularly among less‐hopeful mothers, and interventions to reappraise uncertainty, may be helpful in promoting coping efficacy. [ABSTRACT FROM AUTHOR]

Aim: Ataluren has been approved for treating nonsense mutation Duchenne muscular dystrophy (nmDMD), and there are currently discussions concerning drug access and applications beyond the development programme. This study provides an overview of nmDMD and ataluren, stipulates clinical rules for treatment initiation and discontinuation and proposes a model for the implementation of orphan drugs in clinical practice in Sweden.Methods: This was a targeted mini-review of the literature from 1995 to 2018, which included cohort studies, guidelines, randomised clinical trials, clinical commentaries and reviews. The review covered the pathophysiology, epidemiology and burden of nmDMD and the clinical programme for ataluren.Results: Based on the current evidence, and our experiences, we recommend that patients with nmDMD should be given ataluren as soon as possible after diagnosis and this treatment should continue until they reach a forced vital capacity of <30%, and, or, a score of at least six on the Brooke upper extremity scale. We propose an implementation model that comprises a coordinating specialist physician and a national expert committee responsible for providing clinical intelligence to ensure appropriate use.Conclusion: Our clinical recommendations and proposed implementation model will inform the optimum medical management of nmDMD in Sweden and help ensure timely, equal access to ataluren and similar orphan drugs. [ABSTRACT FROM AUTHOR]

Aim: To develop a patient-reported outcome measure that comprehensively captures the health-related priorities of children with Duchenne muscular dystrophy (DMD).Method: Children with DMD and their parents completed the iteratively revised versions of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD), followed by a cognitive interview to develop a pilot version of a new measure. Multidisciplinary health care professionals completed an item-by-item analysis of the measure and a 14-item sensibility questionnaire. Minimum content validity ratio for each item of the new measure and the mean score (0-7) for the items of the sensibility questionnaire were calculated.Results: The CPCHILD underwent changes over 19 interviews with children and their parents, resulting in the pilot Muscular Dystrophy Child Health Index of Life with Disabilities (MDCHILD). The content validity ratio of each MDCHILD item ranged from 0.85 to 1 based on health care professionals' ratings. The mean score exceeded the threshold of four for all items of the sensibility questionnaire. Based on child, parent, and health care professional recommendations, 16 items were added, six eliminated, and 15 items modified from the original CPCHILD. The MDCHILD consists of 47 items over seven domains.Interpretation: The MDCHILD met all sensibility criteria by children with DMD, their parents, and health care professionals, and is ready for psychometric evaluation.What This Paper Adds: The Muscular Dystrophy Child Health Index of Life with Disabilities (MDCHILD) is a new patient-reported outcome measure for Duchenne muscular dystrophy (DMD). The Priority Framework of Outcomes underpins the content for the MDCHILD. The MDCHILD incorporates the health-related priorities of males with DMD and their parents. The MDCHILD was deemed sensible by children, their parents, and health care professionals. [ABSTRACT FROM AUTHOR]

Population studies of rare disorders, such as Duchenne and Becker muscular dystrophies (dystrophinopathies), are challenging due to diagnostic delay and heterogeneity in disorder milestones. To address these challenges, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) in 2002 in the United States. From 2002 to 2012, MD STARnet longitudinally tracked the prevalence, clinical, and health care outcomes of 1054 individuals born from 1982 to 2011 with pediatric-onset dystrophinopathy through medical record abstraction and survey data collection. This article summarizes 31 MD STARnet peer-reviewed publications. MD STARnet provided the first population-based prevalence estimates of childhood-onset dystrophinopathy in the United States. Additional publications provided insights into diagnostic delay, dystrophinopathy-specific growth charts, and health services use. Ongoing population-based surveillance continually improves our understanding of clinical and diagnostic outcomes of rare disorders. [ABSTRACT FROM AUTHOR]

Goal: We evaluated the potential for prenatal diagnosis of merosin-negative muscular dystrophies by immunohistochemistry. Materials and Methods: This is a retrospective study of 12 pregnancies with merosin-negative muscular dystrophy in a prior child. Chorionic villus sampling (CVS) was performed between 11th to 13th gestational weeks. Merosin immunohistochemical studies were performed on trophoblastic cells. Results: Two of 12 were "merosin-negative," both were from the same family. Fetal ultrasonographies were evaluated as normal in these pregnancies. Eight of the 10 merosin-positive cases delivered healthy babies. Two were lost to follow-up. Conclusion: Prenatal diagnosis of merosin-negative muscular dystrophies can be accomplished by immunohistochemical analysis. [ABSTRACT FROM AUTHOR]

Introduction: Duchenne muscular dystrophy (DMD) is a devastating, progressive neuromuscular disorder for which there is no cure. As the dystrophin gene is located on the X chromosome, DMD occurs predominately in males. DMD is caused by a lack of functional dystrophin protein resulting from mutations in the 2.2-Mb DMD gene, whichdisrupts the reading frame. Care considerations for DMD advocate a coordinated, multidisciplinary approach to the management of DMD in order to optimize management of the primary manifestations of DMD as well as any secondary complications that may arise.Methods: This review provides an overview of the multidisciplinary clinical management of DMD with regard to the respiratory, cardiology, orthopedic, and nutritional needs of patients with DMD. Recent advances in novel disease-modifying treatments for DMD are also discussed with specific reference to exon skipping and suppression of premature stop codons as promising genetic therapies.Results: The combination of multidisciplinary clinical management alongside novel gene therapiesoffers physicians a powerful armamentarium for the treatment of DMD. [ABSTRACT FROM AUTHOR]

Background and purpose: Duchenne muscular dystrophy (DMD) is a lethal progressive pediatric muscle disorder and genetically inherited as an X-linked disease that caused by mutations in the dystrophin gene. DMD leads to progressive muscle weakness, degeneration, and wasting; finally, follows with the premature demise in affected individuals due to respiratory and/or cardiac failure typically by age of 30. For decades, scientists tried massively to find an effective therapy method, but there is no absolute cure currently for patients with DMD, nevertheless, recent advanced progressions on the treatment of DMD will be hopeful in the future. Several promising gene therapies are currently under investigation. These include gene replacement, exon skipping, suppression of stop codons. More recently, a promising gene editing tool referred to as CRISPR/Cas9 offers exciting perspectives for restoring dystrophin expression in patients with DMD. This review intents to briefly describe these methods and comment on their advances. Since DMD is a genetic disorder, it should be treated by replacing the deficient DMD copy with a functional one. However, there are different types of mutations in this gene, so such therapeutic approaches are highly mutation specific and thus are personalized. Therefore, DMD has arisen as a model of genetic disorder for understanding and overcoming of the challenges of developing personalized genetic medicines, consequently, the lessons learned from these approaches will be applicable to many other disorders. Conclusions: This review provides an update on the recent gene therapies for DMD that aim to compensate for dystrophin deficiency and the related clinical trials. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder. It is still an incurable disease and many clinical trials are going on to find the cure for this disease. There is a need for sensitive and reliable measures for detecting the disease progression. This manuscript focuses on reviewing the different outcome measures which can be used in the Indian DMD patients. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is commonly seen in patients with Duchenne muscular dystrophy (DMD). Few studies have shown a correlation between loss of different isoforms of the DMD gene and cognitive impairment. Objective: The objective of the study was to determine whether correlation exists in the location of mutation in DMD gene or loss of different isoforms and cognitive impairment in children with DMD in the Indian population. Materials and Methods: Ten children were evaluated. Gene mutation analysis was done by multiplex ligation-dependent probe amplification method. The isoforms affected were inferred from mutation location in each of these patients. Binet Kamat Intelligence Test (BKT) and Bender Gestalt test (BGT) were administered. Results: All male patients were aged between 4 and 9 years. Genetic analysis showed deletion in all patients, with seven having deletion in “hotspot” regions (exon 43–52). Psychometric analysis by BGT and BKT showed mean score of 8.6 and mean IQ score of 85.5, respectively. Comparison between patients with hotspot mutations and mutations in other regions, for mean IQ score and BGT score, was statistically significant (P = 0.132 and P = 0.005, respectively). The difference in the IQ score between patients with isolated Dp427 loss (n = 3) and cumulative Dp427/Dp260/Dp140utr loss (n = 6) was statistically significant (P = 0.011). Visuomotor functioning was more impaired in patients with isolated Dp427 loss. Conclusion: The role of cumulative loss of isoforms along with importance of loss of Dp140pc isoform was seen in our study. One patient with loss of Dp140utr isoform had intellectual impairment which is not commonly seen. Visuomotor functioning is more affected in more upstream mutations as shown in our study. [ABSTRACT FROM AUTHOR]

Introduction Few long-term cohort studies have addressed changes in the ambulatory capacity of patients with Duchenne muscular dystrophy (DMD), and no reports have evaluated the factors associated with ambulatory capacity in Japanese. Methods The longitudinal changes in 10-meter run/walk ability and associated factors were retrospectively investigated using general practice data. The factors associated with loss of this ability before the age of 10 years were explored by logistic regression analysis using parameters of genetic mutations, corticosteroid use, the manual muscle test (MMT), and the joint range of motion (ROM). Explanatory variables of MMT grade included hip flexors, knee flexors, and knee extensors; ROM included hip extension, knee extension, and ankle dorsiflexion. Results Among 418 patients diagnosed with DMD, 145 patients underwent the 10-meter run/walk test between March 1999 and July 2015. The median age at loss of 10-meter walking ability was 10.4 (interquartile range: 9.2–11.3) years. The 10-meter run/walk speed began to decline 3 years before the loss of 10-meter walking ability, and the median was <1 m/s 1 year before the loss of 10-meter walking ability. MMT grade for knee flexors and ROM for hip and knee extension were identified as independent predictors. Based on the change over time of these three items, limitation of the hip extension ROM preceded knee flexor weakness and limitation of the knee extension ROM. Conclusions This knowledge can be used in optimizing rehabilitation programs and evaluating effect of treatment for DMD patients. [ABSTRACT FROM AUTHOR]

This study introduces local pattern texture anisotropy as a novel parameter to differentiate healthy and disordered muscle and to gauge the severity of muscle impairments based on B-mode ultrasound images. Preliminary human results are also presented. A local pattern texture anisotropy index (TAI) was computed in one region of interest in the short head of the biceps brachii. The effects of gain settings and box sizes required for TAI computation were investigated. Between-day reliability was studied in patients with sporadic inclusion body myositis (n = 26). The ability of the TAI to discriminate dystrophic from healthy muscle was evaluated in patients with Duchenne muscular dystrophy and healthy controls (n = 16). TAI values were compared with a gray-scale index (GSI). TAI values were less influenced by gain settings than were GSI values. TAI had lower between-day variability (typical error = 2.3%) compared with GSI (typical error = 2.3% vs. 8.3%, respectively). Patients with Duchenne muscular dystrophy had lower TAIs than controls (0.76 ± 0.06 vs. 0.87 ± 0.03, respectively, p <0.05). At 40% gain, TAI values correlated with percentage predicted elbow flexor strength in inclusion body myositis (R = 0.63, p <0.001). The TAI may be a promising addition to other texture-based approaches for quantitative muscle ultrasound imaging. [ABSTRACT FROM AUTHOR]

Background: Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. We designed this study to determine the prevalence of left bundle branch block (LBBB), whether there is a relationship between LBBB and genetic pattern, and to assess predictive factors for acute cardiac events and mortality in adult DMD patients. Methods: We reviewed the charts of DMD followed at the Home Mechanical Ventilation Unit of the Raymond Poincare University Hospital. Results: A total of 121 patients, aged from 18 to 41 years have been included in our study. Median vital capacity (VC) was 12% [7; 19.5] of predicted. Almost all patients were on home mechanical ventilation (95%). LBBB was present in 15 patients (13%); among them, 10 disclosed exonic deletions. After a median follow up of 6 years, 21 patients (17%) experienced acute heart failure (AHF), 7 patients (6%) supraventricular arrhythmia, 3 patients (2.4%) ventricular tachycardia, 4 patients (3%) significant electrical disturbances. LBBB was significantly associated with cardiac events (OR = 12.7; 95%CI [3.78–42.7]; p <0.0001) and mortality (OR = 4.4; 95%CI [1.44–13.7]; p 0.009). Presence of residual dystrophin protein was not associated with significant less cardiac events. Age and LVEF were also predictive factors for cardiac events and mortality. Conclusion: LBBB is relatively frequent in DMD and is a major predictive factor for cardiac events and mortality. Presence of residual dystrophin protein was not associated with a lower incidence of cardiac events. [ABSTRACT FROM AUTHOR]

The development of new therapeutic agents for the treatment of Duchenne muscular dystrophy has put a focus on defining outcome measures most sensitive to capture treatment effects. This cross-sectional analysis investigates the relation between validated clinical assessments such as the 6-minute walk test, motor function measure and quantitative muscle MRI of thigh muscles in ambulant Duchenne muscular dystrophy patients, aged 6.5 to 10.8 years (mean 8.2, SD 1.1). Quantitative muscle MRI included the mean fat fraction using a 2-point Dixon technique, and transverse relaxation time (T2) measurements. All clinical assessments were highly significantly inter-correlated with p < 0.001. The strongest correlation with the motor function measure and its D1-subscore was shown by the 6-minute walk test. Clinical assessments showed no correlation with age. Importantly, quantitative muscle MRI values significantly correlated with all clinical assessments with the extensors showing the strongest correlation. In contrast to the clinical assessments, quantitative muscle MRI values were highly significantly correlated with age. In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration. [ABSTRACT FROM AUTHOR]

Copyright of Neurosciences is the property of Neurosciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Duchenne muscular dystrophy ( DMD) is an X-linked muscle disorder characterized by progressive, irreversible loss of cardiac and skeletal muscular function. Muscular enlargement in DMD is attributed to oedema, due to the increased cytoplasmic Na+ concentration. The aim of this review was to present the current experience and emphasize the role of cardiovascular magnetic resonance ( CMR) in the diagnosis of this condition. DMD patients' survival depends on ventilatory assistance, as respiratory muscle dysfunction was the most common cause of death in the past. Currently, due to improved ventilatory assistance, cardiomyopathy has become the main cause of death, even though clinically overt heart failure may be absent. CMR is the technique of choice to assess the pathophysiologic phenomena taking place in DMD, such as myocardial oedema and subepicardial fibrosis. The classic index to assess oedema is the T2-weighted short-tau inversion recovery (T2w- STIR), as it suppresses the signal from flowing blood and resident fat and enhances sensitivity to tissue fluid. Furthermore, CMR is the most reliable technique to detect and quantify fibrosis in DMD. Recently, the new indices T2, T1 mapping (native and postcontrast) and the extracellular volume ( ECV) allow a more accurate approach of myocardial oedema and fibrosis. To conclude, the assessment of cardiac oedema and subepicardial fibrosis in the inferolateral wall of the left heart ventricle are the most important early finding in DMD with preserved ventricular function, and CMR, using both the classic and the new indices, is the best technique to detect and monitor these lesions. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy ( DMD) is an X-linked muscle disorder characterized by progressive and irreversible loss of muscular function. As muscular disease progresses, the repair mechanisms cannot compensate for cellular damage, leading inevitably to necrosis and progressive replacement by fibrous and fatty tissue. Cardiomyopathy and respiratory failure are the main causes of death in DMD. In addition to the well-described muscle and heart disease, cognitive dysfunction affects around 30% of DMD boys. Myocardial fibrosis, assessed by late gadolinium enhancement ( LGE), using cardiovascular magnetic resonance imaging ( CMR), is an early marker of heart involvement in both DMD patients and female carriers. In parallel, brain MRI identifies smaller total brain volume, smaller grey matter volume, lower white matter fractional anisotropy and higher white matter radial diffusivity in DMD patients. The in vivo brain evaluation of mdx mice, a surrogate animal model of DMD, showed an increased inorganic phosphate (P(i))/phosphocreatine ( PCr) and pH. In this paper, we propose a holistic approach using techniques of magnetic resonance imaging, spectroscopy and diffusion tensor imaging as a tool to create a 'heart and brain imaging map' in DMD patients that could potentially facilitate the patients' risk stratification and also future research studies in the field. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by an absence of the 427kD muscle-specific dystrophin isoform. Utrophin is the autosomal homolog of dystrophin and when overexpressed, can compensate for the absence of dystrophin and rescue the dystrophic phenotype of the mdx mouse model of DMD. Utrophin is subject to miRNA mediated repression by several miRNAs including let-7c. Inhibition of utrophin: let-7c interaction is predicted to 'repress the repression' and increase utrophin expression. We developed and tested the ability of an oligonucleotide, composed of 2'-O-methyl modified bases on a phosphorothioate backbone, to anneal to the utrophin 3'UTR and prevent let-7c miRNA binding, thereby upregulating utrophin expression and improving the dystrophic phenotype in vivo. Suppression of utrophin: let-7c interaction using bi-weekly intraperitoneal injections of let7 site blocking oligonucleotides (SBOs) for 1 month in the mdx mouse model for DMD, led to increased utrophin expression along with improved muscle histology, decreased fibrosis and increased specific force. The functional improvement of dystrophic muscle achieved using let7-SBOs suggests a novel utrophin upregulation-based therapeutic strategy for DMD. [ABSTRACT FROM AUTHOR]

Many studies have evaluated surgical treatments for spinal deformities in patients with neuromuscular disease. However, few reports have described patients with Fukuyama congenital muscular dystrophy (FCMD). A 13-year-old boy with FCMD was unable to sit for long periods or sleep in the supine position because of progressive scoliosis. His Cobb angle worsened from 27° to 41° in 5 months. He underwent standard posterior spinal fusion and pedicle-screw-alone fixation from T5 to S1. Postoperatively, his Cobb angle improved from 41° to 25° without exacerbation for 2 years. After the surgery, he was able to sit for longer periods without pain, and he and his family were satisfied with the efficacy of the spinal fusion. Some patients with mild FCMD can sit at the age of puberty, but progression to scoliosis is possible. Therefore, spinal fusion for progressive scoliosis in patients with FCMD should be considered. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy. In a Brazilian golden retriever muscular dystrophy (GRMD) dog colony, two related dogs demonstrated strikingly mild dystrophic phenotypes compared with those typically observed in severely affected GRMD dogs despite lacking dystrophin. Microarray analysis of these "escaper" dogs revealed reduced expression of phosphatidylinositol transfer protein-α (PITPNA) in escaper versus severely affected GRMD dogs. Based on these findings, we decided to pursue investigation of modulation of PITPNA expression on dystrophic pathology in GRMD dogs, dystrophin-deficient sapje zebrafish, and human DMD myogenic cells. In GRMD dogs, decreased expression of Pitpna was associated with increased phosphorylated Akt (pAkt) expression and decreased PTEN levels. PITPNA knockdown by injection of morpholino oligonucleotides in sapje zebrafish also increased pAkt, rescued the abnormal muscle phenotype, and improved long-term sapje mutant survival. In DMD myotubes, PITPNA knockdown by lentiviral shRNA increased pAkt and increased myoblast fusion index. Overall, our findings suggest PIPTNA as a disease modifier that accords benefits to the abnormal signaling, morphology, and function of dystrophic skeletal muscle, and may be a target for DMD and related neuromuscular diseases. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether in-the-moment diary reports of daily experience, taken collectively, are a valid representation of health-related quality of life (HRQL).Methods: A total of 35 boys with Duchenne muscular dystrophy (DMD) were recruited through four neuromuscular care providers across Australia. Participants completed the PedsQL™ Generic Core scales and one week of experience-sampling diary reporting on a personal digital assistant. Rasch analysis was undertaken on the diary data to derive a single valid measure score. The resulting measure score for each participant was correlated with the summary score from the PedsQL™ Generic Core scales to examine whether daily experience was representative of HRQL.Results: The daily diary method showed good metric properties, with adequate goodness of fit for data from items and participants suggesting unidimensionality of the construct: quality of everyday experience. The correlation of the daily diary measure score with overall PedsQL™ summary score showed moderate agreement (r = .60, p = 0.001).Conclusions: The benefits of measuring daily quality of life include detailed descriptions of day-to-day experiences of children without the need for retrospective recall. Diary methods on an electronic platform or software application for personal devices may be a useful tool to understand HRQL as the repeated measures data provide a detailed experience directly from the child and the platform makes data completion highly motivating. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy leads to cardiomyopathy. The objective of this study was to estimate the association of body mass index with cardiomyopathy onset. Cardiomyopathy was defined as left ventricular ejection fraction <55% or left ventricular fractional shortening <28%. Overall, 48% met the criteria for cardiomyopathy. We were unable to demonstrate an association between body mass index Z score and age of cardiomyopathy onset (hazard ratio 0.79, 95% confidence interval 0.57-1.11, P = .17) after adjusting for covariates. Duration of corticosteroid use (P = .01), but not loss of ambulatory ability (P = .47), was associated with age of cardiomyopathy onset. We were unable to detect a significant difference in median body mass index Z scores in corticosteroid-treated boys compared with corticosteroid-naïve boys (1.11, 95% confidence interval 0.25-1.95, vs 1.05, 95% confidence interval 0.01-1.86, P = .69). No association was detected between the body mass index Z scores of Duchenne muscular dystrophy subjects and age of cardiomyopathy onset. [ABSTRACT FROM AUTHOR]

Aim: To develop a patient-reported outcome measure (PROM) assessing upper limb function related to activities of daily living (ADL) that cannot be observed in a clinical setting, specifically for patients with Duchenne muscular dystrophy (DMD) across a wide age range, applicable in the different stages of the disease.Method: The developmental process was based on US Food and Drug Administration guidelines. This included item generation from a systematic review of existing tools and expert opinion on task difficulty and relevance, involving individuals with DMD. Cultural aspects affecting ADL were taken into consideration to make this tool applicable to the broad DMD community. Items were selected in relation to a conceptual framework reflecting disease progression covering the full range of upper limb function across different ADL domains.Results: After pilot testing and iterative Rasch analyses, redundant or clinically irrelevant items were removed. The final questionnaire consists of 32 items covering four domains of ADL (food, self-care, household and environment, leisure and communication). Test-retest reliability was excellent.Interpretation: A DMD-specific upper limb PROM was developed on the basis of clinical relevance and psychometric robustness. Its main purpose is to document the patient self-reported natural history of DMD and assess the efficacy of interventions. [ABSTRACT FROM AUTHOR]

Research has indicated that over 50% of caregivers for children with Duchenne Muscular Dystrophy (DMD) lack adequate knowledge about the respiratory system, the diagnosis of related disorders, supportive methods, and treatment options. Moreover, GP doctors also possess limited knowledge about potential respiratory complications and appropriate treatments. Consequently, individuals with DMD in Poland are not receiving the necessary respiratory support. Many caregivers are hesitant to implement non-invasive ventilation due to its association with the advanced stage of the disease. To address the respiratory needs of patients with chronic and immobilizing conditions like DMD, e-health can serve as a valuable means of support. The two primary components of e-Health, namely telemedicine and mobile health, offer promising applications in the field of medicine. It is evident that there is a pressing need to establish standardized protocols for the management of DMD patients concerning diagnosis, monitoring, and respiratory support. It is crucial to develop comprehensive algorithms for patients, their families, as well as healthcare professionals, including doctors and other care providers. Conclusions: there is a need to establish standardized guidelines for the management of DMD patients in the field of diagnostics, monitoring, and respiratory support. Algorithms for patients and their families, as well as for doctors and other health care professionals, should be created. [ABSTRACT FROM AUTHOR]

Patients with Duchenne muscular dystrophy are less physically active than their healthy peers. It is widely known that the physical activity of parents strongly correlates with the physical activity of their children, both with disabilities and healthy. Results of the pilot study revealed a low level of physical activity in mothers of children with Duchenne muscular dystrophy regardless of whether the mother was a carrier of the dystrophin gene or not. The online survey was completed by 50 respondents. Almost 60% of them, had no regular physical activity, and only 22% walked continuously for longer than 10 minutes per day. Moreover the study showed that, similarly to other mothers of children with chronic progressive diseases, they demonstrate a high level of anxiety (70% of respondents). From the study group, 90% of respondents declared that they would attend physical activity classes under the condition to receive organized care for their children during that time. The abovementioned declaration indicates the need for institutional coordinated support for mothers of Duchenne muscular dystrophy that will help to implement regular physical activity in their lives. As numerous studies report exercise may reduce anxiety. Moreover, strength, endurance, and mobility are crucial parameters for the caregiver of a child with a severe disability to reduce the risk of spine and other musculoskeletal injuries and remain healthy for long years. [ABSTRACT FROM AUTHOR]

Duchenne Muscular Dystrophy (DMD) is caused by mutations in the dystrophin gene leading to dystrophin deficiency, muscle fiber degeneration and progressive fibrotic replacement of muscles. Givinostat, a histone deacetylase (HDAC) inhibitor, significantly reduced fibrosis and promoted compensatory muscle regeneration in mdx mice. This study was conducted to evaluate whether the beneficial histological effects of Givinostat could be extended to DMD boys. Twenty ambulant DMD boys aged 7 to <11 years on stable corticosteroid treatment were enrolled in the study and treated for ≥12 months with Givinostat. A muscle biopsy was collected at the beginning and at the end of treatment to evaluate the amount of muscle and fibrotic tissue. Histological effects were the primary objectives of the study. Treatment with Givinostat significantly increased the fraction of muscle tissue in the biopsies and reduced the amount of fibrotic tissue. It also substantially reduced tissue necrosis and fatty replacement. Overall the drug was safe and tolerated. Improvement in functional tests was not observed in this study, but the sample size of the study was not sufficient to draw definitive conclusions. This study showed that treatment with Givinostat for more than 1 year significantly counteracted histological disease progression in ambulant DMD boys aged 7 to 10 years. [ABSTRACT FROM AUTHOR]

Preserving upper extremity (UE) function in patients with Duchenne muscular dystrophy (DMD) is extremely important as it is related to independence and quality of life. For clinical decision making, knowledge of variables associated with UE function is necessary. This knowledge is, however, limited. Therefore, this study aims to gain more insight into the variables associated with UE function in DMD. Data from an international web-based questionnaire on UE function, obtained from 213 DMD patients, were used. Six dependent variables regarding UE function were used in multivariable linear regression analyses. In addition, 26 independent variables regarding patient characteristics, medication, therapy, supportive aids, pain, stiffness and participation were used. Twelve independent variables showed a significant relation to UE function. Variables with a negative relation to UE function were: later disease stage, occurrence of scoliosis, higher age, use of UE splints, more frequent stiffness complaints, more limitations due to stiffness, more frequent elbow pain, and having physical therapy. A positive relation with UE function was seen for going to school or work, use of corticosteroids, higher BMI, and higher age at diagnosis. These variables explained 56-81 % of the variation of the different measures of UE function. Knowledge of variables associated with UE function is very important in the clinical management of DMD patients. The results of this study suggest that corticosteroid use and participation in school and work related activities are positively related to UE function in DMD patients, as well as reducing pain and stiffness and preventing scoliosis. [ABSTRACT FROM AUTHOR]

Study Design: A cross-sectional analysis.Objective: The aim of this study was to determine whether the surgical treatment for scoliosis due to Duchenne muscular dystrophy (DMD) has decreased over a recent 11-year period, specifically, after the wide acceptance of glucocorticoid treatment for DMD.Summary Of Background Data: DMD can result in a flaccid neuromuscular scoliosis that has been traditionally treated surgically. In 2004, a comparative study demonstrated that glucocorticoid treatment decreased the progression of scoliosis in DMD.Methods: We used the Nationwide Inpatient Sample from 2001 to 2012 to identify patients with DMD undergoing spinal fusion. Demographic information (age, hospital size, location, geographic status) was collected. We examined the distribution of patient and hospital characteristics among cohorts undergoing spinal fusion from 2001 to 2004 (period 1; before publication of the comparative study), 2005 to 2008 (period 2; immediately following publication of the comparative study), and 2009 to 2012 (period 3; moderate duration following publication of the comparative study).Results: We identified 1874 males undergoing spinal fusion. During this period, the overall rate of DMD surgeries declined by 48%-from 1.87 surgeries in 2001 to 0.97 surgeries in 2012 per million US males per year. This decline was significantly pronounced following the publication of the comparative study [periods 2 and 3; For period 2 vs. period 1: incidence rate ratio (IRR) = 0.71, 95% confidence interval (95% CI) = 0.56-0.91, P = 0.01; For period 3 vs. period 1: IRR = 0.77, 95% CI = 0.61-0.97, P = 0.03].Conclusion: Our study demonstrates a significant decrease in the rate of scoliosis surgery for DMD from 2001 to 2012. It appears that the decline in surgical treatment could be related to the publication and landmark study demonstrating decreased progression of scoliosis with glucocorticoid treatment.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Background: Facioscapulohumeral muscular dystrophy (FSHD; OMIM 158900 & 158901) is a progressive skeletal muscle dystrophy, characterized by an autosomal dominant inheritance pattern. One of the major unsolved questions in FSHD is the marked clinical heterogeneity, ranging from asymptomatic individuals to severely affected patients with an early onset. An estimated 10% of FSHD patients have an early onset (onset before 10 years of age) and are traditionally classified as infantile FSHD. This subgroup is regarded as severely affected and extra-muscular symptoms, such as hearing loss and retinopathy, are frequently described. However, information on the prevalence, natural history and clinical management of early onset FSHD is currently lacking, thereby hampering adequate patient counselling and management. Therefore, a population-based prospective cohort study on FSHD in children is highly needed.Methods/design: This explorative study aims to recruit all children (aged 0-17 years) with a genetically confirmed diagnosis of FSHD in The Netherlands. The children will be assessed at baseline and at 2-year follow-up. The general aim of the study is the description of the clinical features and genetic characteristics of this paediatric cohort. The primary outcome is the motor function as measured by the Motor Function Measure. Secondary outcomes include quantitative and qualitative description of the clinical phenotype, muscle imaging, genotyping and prevalence estimations. The ultimate objective will be a thorough description of the natural history, predictors of disease severity and quality of life in children with FSHD.Discussion: The results of this population-based study are vital for adequate patient management and clinical trial-readiness. Furthermore, this study is expected to provide additional insight in the epigenetic and environmental disease modifying factors. In addition to improve counselling, this could contribute to unravelling the aetiology of FSHD.Trial Registration: clinicaltrials.gov NCT02625662. [ABSTRACT FROM AUTHOR]

We conducted a study to evaluate the quality of life in boys with Duchenne muscular dystrophy aged 8–18 years, compared with that in matched healthy controls. A total of 85 boys with Duchenne muscular dystrophy aged 8–18 years and 136 age, sex and living place matched healthy controls were included in this study. Patients and one of their parents separately completed the 27-item Persian version of KIDSCREEN questionnaire (child and adolescent version and parent version). From the children's perspective, the quality of life in patients was found to be lower in two subclasses: “physical activities and health” (p < 0.001) and “friends” (p = 0.005). Parental estimation of their sick child's quality of life was significantly lower than children's own assessment in two subclasses: “physical activities and health” (p < 0.001) and “general mood and feelings” (p < 0.001). Our results indicate that boys with Duchenne muscular dystrophy have quite a satisfactory quality of life. A happier and more hopeful life can be promoted through increasing social support and improving the parental knowledge regarding their child's more positive life perspective. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying mutations using new gene-editing technologies and corticosteroid analogs with better safety profiles offers renewed hope for many individuals with DMD and their families. [ABSTRACT FROM AUTHOR]

This study investigated clinical and family characteristics associated with health-related quality of life in children with Duchenne muscular dystrophy. Families of 176 boys with Duchenne muscular dystrophy were identified and mailed questionnaires via the Canadian Neuromuscular Disease Registry. Multiple linear regressions analyses were used to examine the relationship between clinical and family characteristics and child-self and parent-proxy reported health-related quality of life. Greater fatigue and use of wheelchairs were consistently associated with worse health-related quality of life independent of other factors. Higher household income and parent having a postsecondary degree were associated with better health-related quality of life in some of the measures. A greater clinical focus on and efforts to reduce fatigue could lead to improvement of health-related quality of life in the Duchenne muscular dystrophy population. This study also sets the ground for longitudinal studies where changes in health-related quality of life can be monitored over time. [ABSTRACT FROM AUTHOR]

Objective This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials. Methods Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis. Results Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit–risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain. Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers. Conclusions The majority of parents described undertaking benefit–risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm. [ABSTRACT FROM AUTHOR]

Introduction Duchenne muscular dystrophy (DMD) is a fatal progressive muscle wasting disease considered untreatable since its first description in 1868. In 1987, the dystrophin gene responsible for DMD was cloned. This paved the way for the development of therapies. Antisense oligonucleotide (AO)-mediated exon skipping therapy is now reaching the stage of marketing authorization. On the 20th anniversary of the proposal of AO-mediated exon skipping therapy for DMD, this review explores the contributions of Japanese patients. Results In 1990, a Japanese DMD patient was reported as having a small deletion within dystrophin exon 19 and complicating exon 19 skipping in the absence of any mutation at the consensus splice sites. This led to identification of a splicing enhancer sequence within exon 19. Remarkably, AOs against this sequence were shown to induce exon skipping. This encouraged us to propose AO-mediated exon skipping therapy for DMD in 1995. The therapy’s effectiveness was verified in a Japanese patient with a nonsense dystrophin mutation manifesting as Becker muscular dystrophy. The patient showed skipping of the nonsense mutation-encoding exon. Finally, a DMD patient carrying a deletion of exon 20 volunteered to undergo intravenous AO infusion, enabling us to obtain proof of concept. The findings from these three patients greatly facilitated studies on exon skipping therapy. As a result, more than 300 reports on AO-mediated exon skipping therapy for DMD have been published, including at least two a month during the last few years. Conclusion We greatly appreciate the important contributions of Japanese patients to development of the exon skipping therapy for DMD. [ABSTRACT FROM AUTHOR]

New Findings What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy., What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches., Duchenne muscular dystrophy is a lethal X-linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene-replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re-establish muscle function. [ABSTRACT FROM AUTHOR]

Objectives: Duchenne muscular dystrophy (DMD) is the most common and severe dystrophinopathy. DMD carriers rarely present with clinical symptoms, but may suffer from cardiac involvement. Because echocardiographic findings are inconsistent and cardiac magnetic resonance imaging (CMRI) data are limited, this study sought to investigate asymptomatic carriers for cardiac abnormalities using CMRI. Methods: Fifteen genetically confirmed DMD carriers (age, 32.3 ± 10.2 years) were prospectively examined on a 1.5T MR system. Cine, T2, and late-gadolinium-enhanced (LGE) images were acquired, and were evaluated in consensus by two experienced readers. Left ventricular (LV) parameters were analysed semiautomatically, normalized to BSA. Results: Normalized LV end-diastolic volume was increased in 7 % (73.7 ± 16.8 ml/m; range, 48-116 ml/m) and normalized LV end-systolic volume in 20 % (31.5 ± 13.3 ml/m; range, 15-74 ml/m). EF was reduced in 33 % (58.4 ± 7.6 %; range, 37-69 %) and normalized LV myocardial mass in 80 % (40.5 ± 6.8 g/m; range, 31-55 g/m). In 80 %, regional myocardial thinning was detected in more than one segment. In 13 % and 40 %, apical-lateral accentuation of LV non-compaction was present. LGE was found in 60 % (midmyocardial inferolateral accentuation). Conclusions: Given the high frequency of cardiac pathologies detected by CMRI, regular cardiac risk assessment is advisable for DMD carriers. Besides clinical examination, CMRI is an excellent tool for this purpose. Key Points: • Fifteen Duchenne muscular dystrophy carriers investigated using CMRI all showed cardiac pathologies. • Myocardial mass reduction, regional myocardial thinning, and late gadolinium enhancement were common. • Regular cardiac risk assessment is thus advisable in Duchenne muscular dystrophy carriers. • Besides clinical examination, CMRI is an excellent tool for this purpose. [ABSTRACT FROM AUTHOR]

Communicating about Duchenne muscular dystrophy and its prognosis can be difficult for affected children and their family. We focused on how physicians provide support to the mothers of children with Duchenne muscular dystrophy who have difficulty communicating about the condition with their child. The eligible participants were certified child neurologists of the Japanese Society of Child Neurology. Participants responded to questionnaires consisting of free descriptions of a vignette of a child with Duchenne muscular dystrophy and a mother. We analyzed 263 responses of the participants. We found 4 themes on advising mothers, involving encouraging communication, family autonomy, supporting family, and considering the child’s concerns. These results provide a better understanding of the communication between physicians and family members who need help sharing information with a child with Duchenne muscular dystrophy. These findings will assist clinical practitioners in supporting families and the affected children throughout the course of their illness. [ABSTRACT FROM AUTHOR]

This population-based study examines the association between corticosteroid treatment and time to loss of ambulation, stratifying by treatment duration (short: 0.25-3 years, long: >3 years), among 477 Duchenne muscular dystrophy cases identified by the Muscular Dystrophy Surveillance Tracking and Research Network (MDSTARnet). Those cases who received short-term corticosteroid treatment had a time to loss of ambulation that was 0.8 years shorter (t test) and an annual risk of losing ambulation 77% higher than the untreated (Cox regression). Conversely, cases who received long-term corticosteroid treatment had a time to loss of ambulation that was 2 years longer and an annual risk of losing ambulation 82% lower than the untreated, up to age 11 years; after which the risks were not statistically different. The relationship of corticosteroids and time to loss of ambulation is more complex than depicted by previous studies limited to treatment responders or subjects who lost ambulation during study follow-up. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed 2030 childhood electromyograms performed over an 11-year period (2004-2014). Twenty children (1%) with myotonic discharges were identified and placed into 2 groups. Group A (electrical and clinical myotonia) comprised 9 children (8 with myotonia congenita and 1 with paramyotonia congenita); all of them had diffuse myotonic discharges without clinical weakness or elevated creatine kinase. Group B (electrical myotonia without clinical myotonia) comprised 11 children (4 with inflammatory myopathy; 3, congenital myopathy, 3, muscular dystrophy; and 1, congenital muscular dystrophy). Clinical weakness was demonstrated in all of them and elevated creatine kinase in 6; all had a myopathic electromyogram and scattered myotonic discharges. We conclude that myotonic discharges are a rare but characteristic spontaneous discharge identified during electrodiagnostic studies in children. The presence of electrical and clinical myotonia provides helpful clues to differentiate between various muscle disorders in children. [ABSTRACT FROM AUTHOR]

Key Clinical Message Walker-Warburg syndrome is a rare congenital disorder. Several features, including muscular dystrophy, hydrocephalus, and oropharyngeal abnormalities, have important implications in the perioperative setting. We present a case of general anesthesia in an infant and discuss perioperative considerations to guide clinicians faced with the management of patients with this syndrome. [ABSTRACT FROM AUTHOR]

Purpose: To present the results of ophthalmological examinations in children with muscular dystrophies and highlight the importance of their ophthalmological evaluation. Methods: Retrospective analysis of the ophthalmological examination records in 74 children with a type of muscular dystrophy, examined between January 2011 and January 2015, was performed. Results: The most common type of muscular dystrophy observed in our patients was Duchenne muscular dystrophy (67.5%), followed by Becker muscular dystrophy (9.4%), myotonic dystrophy (8%), limb-girdle muscular dystrophy (6.7%), merosin-negative muscular dystrophy (4%), and Ullrich muscular dystrophy (4%). Ten cases of Duchenne muscular dystrophy had both macular and retinal pigmentary changes (20%) and 9 had abnormal electroretinographies with decreased photopic and scotopic responses. Ptosis was the most common finding (83.3%). No abnormalities of light reflexes, pupil size, or saccadic and smooth pursuit movements were seen among cases with myotonic dystrophy. Conclusions: Ophthalmological problems are commonly seen in children with muscular dystrophies. Simple ophthalmological screening and early intervention can improve their communication skills by way of increasing their visual talents. [ABSTRACT FROM AUTHOR]

Current molecular genomic approaches to human genetic disorders have led to an explosion in the identification of the genes and their encoded proteins responsible for these disorders. The identification of the gene altered by mutations in Duchenne and Becker muscular dystrophy was one of the earliest examples of this paradigm. The nearly 30 years of research partly outlined here exemplifies the road that similar current gene discovery protocols will be expected to travel, albeit much more rapidly owing to improved diagnosis of genetic disorders and an understanding of the spectrum of mutations thought to cause them. The identification of the protein dystrophin has led to a new understanding of the muscle cell membrane and the proteins involved in membrane stability, as well as new candidate genes for additional forms of muscular dystrophy. Animal models identified with naturally occurring mutations and developed by genetic manipulation have furthered the understanding of disease progression and underlying pathology. The biochemistry and molecular analysis of patient samples have led to the different dystrophin-dependent and -independent therapies that are currently close to or in human clinical trials. The lessons learned from decades of research on dystrophin have benefited the field of human genetics. [ABSTRACT FROM AUTHOR]

Objectives: Rigidity of the spine is common in adults but is rarely observed in children. The aim of this study was to report on rigid spine syndrome (RSS) among children in Oman. Methods: Data on children diagnosed with RSS were collected consecutively at presentation between 1996 and 2014 at the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. A diagnosis of RSS was based on the patient's history, clinical examination, biochemical investigations, electrophysiological findings, neuro-imaging and muscle biopsy. Atrophy of the paraspinal muscles, particularly the erector spinae, was the diagnostic feature; this was noted using magnetic resonance imaging of the spine. Children with disease onset in the paraspinal muscles were labelled as having primary RSS or rigid spinal muscular dystrophy. Secondary RSS was classified as RSS due to the late involvement of other muscle diseases. Results: Over the 18-year period, 12 children were included in the study, with a maleto- female ratio of 9:3. A total of 10 children were found to have primary RSS or rigid spinal muscular dystrophy syndrome while two had secondary RSS. Onset of the disease ranged from birth to 18 months of age. A family history was noted, with two siblings from one family and three siblings from another (n = 5). On examination, children with primary RSS had typical features of severe spine rigidity at onset, with the rest of the neurological examination being normal. Conclusion: RSS is a rare disease with only 12 reported cases found at SQUH during the study period. Cases of primary RSS should be differentiated from the secondary type. [ABSTRACT FROM AUTHOR]

Introduction: Duchenne Muscular Dystrophy (DMD) is a genetic neuromuscular disorder with functional disability. In Nepal, eight hundred cases have been registered in Muscular Dystrophy Foundation (MDF). The Survival age of child with Duchene Muscular Dystrophy (DMD) is not more than twenty four years of life. (MDF-Nepal). The purpose of this study was to explore the lived experiences of mothers who are taking care of children with muscular dystrophy. Methods: Using a phenomenological design, nine mothers having DMD children were selected. Data was gathered using In-depth interview method. Respondent's verbal as well as nonverbal clues were recorded during observation. Two to three in-depth interviews were carried out with each respondent along with audio tape recording and field notes. Results: Almost all of the respondents perceived DMD as a progressive fatal form of neuromuscular disease making the child unable to walk by 7-8 years of age. Majority of the respondents had suffered from psychosocial problems as well. The initial reaction of mothers regarding children's diagnosis was a feeling of mixed emotion. Majority of the mothers relieved their anxiety to some extent by sharing their feelings with others, assuring themselves and accepting their reality of their child's illness. Clusters of themes were identified: perception regarding disease, treatment modality, physical mobility of child, and coping mechanisms. Conclusion: Mothers of DMD children are facing a huge array of problems which has decreases the quality of life of mothers. It is recommended to provide, social security, free supply of medicine, health facility and Palliative care for DMD child so that parents may face fewer problems. [ABSTRACT FROM AUTHOR]