Transforming Care of Duchene Muscular Dystrophy in Low-Resource Setting Through Community-Led Initiatives.

The neuropalliative approach in a hospital setting for neuromuscular disorders is essentially multidisciplinary in focus and involves co-ordinated interventions. This case report describes an intensive case management approach through telehealth services provided from a hospital context in South India for psychosocial interventions for an adolescent with Duchenne Muscular Dystrophy. Case management interventions during the COVID-19 pandemic were provided through sixteen sessions over the telephone, focusing on need assessment, service plan development, implementation, co-ordination, and monitoring. Major strategies were crisis management, supportive psychotherapy, and cognitive-behavioural strategies. Adaptations made to meet the challenges of the COVID-19 pandemic using telehealth facilities can be incorporated into routine clinical practice in low-resource settings. IMPLICATIONS Telehealth, which emerged as a viable option for providing effective psychosocial care during the COVID 19 pandemic, could be adopted to complement routine clinical care in low-resource settings.

To explore the relationship between household poverty, inequality, and disability among children in rural Bangladesh. This was a matched case-control study in Shahjadpur, northern Sirajganj, Bangladesh. Children aged younger than 18 years with disabilities (i.e. those with cerebral palsy, spina bifida, hydrocephalus, muscular dystrophy, spinal cord injury, amputation, club foot, cleft lip or palate, trauma or burn-related injury or impairment, congenital deformity, genetic condition, and visual, hearing, and speech impairments) and age-, sex-, and location-matched children without disabilities (i.e. controls) were recruited. Cases were identified using the key informant method. Household poverty likelihood and socioeconomic status (SES) were assessed using a validated poverty scorecard. Descriptive and inferential analyses were completed. Between October 2017 and February 2018, 1274 cases and 1303 controls were recruited (median age at assessment 9 years 10 months [interquartile range 6 years 0 months-13 years 7 months] and 9 years 10 months [5 years 8 months-12 years 0 months] respectively). The household poverty likelihood was 7% higher among cases than controls (p < 0.001). Parental employment, family income, and school enrolment rate were significantly lower among cases than controls especially in the families with low SES. Both underweight and stunting were significantly higher among cases than controls (p < 0.001 for both). Receipt of rehabilitation services and health-care seeking from formal sectors were significantly lower among cases from families with low SES than high SES (60% vs. 71%, p = 0.03; 10% vs. 33%, p < 0.001 respectively). Our findings are crucial to develop interventions and reduce the inequalities between children with and without disabilities in low-resource settings such as Bangladesh as highlighted in the global agenda of the Sustainable Development Goals.

Introduction Early loss-of-ambulation (LOA) and death at young age are inevitable in Duchene muscular dystrophy (DMD). Definite treatment of DMD is not available till date. Prolongation of ambulation and management of complications is the goal of treatment. In sports, high-altitude training is popular to improve athletic performance. We investigated the influence of altitude on DMD in relation to age at LOA. MethodsIt was a cross-sectional study done on 91 DMD patients, who have lost their ambulation, using the database of Muscular Dystrophy Foundation-Nepal. DMD boys living in different elevations of Nepal were divided into &lt;200m (plain), 200-700m (intermediate), 700-1000m (middle), and &gt;1000m (high) groups, and the age at LOA was recorded. Findings were tabulated and analyzed statistically using student's t-test and Log Rank test, with p &lt;0.05 considered significant.ResultsOut of 91 DMD cases registered, 36 (39.6%), 34 (37.4%) were from plain (Terai) area and high land area of Nepal respectively; accounting 77% of the total patients. The median age at LOA for each group increased with elevation, and the LOA age in the high-land group (median ± SD; 11.20 ± 2.78) was significantly higher than that in the low-land group (9.62 ± 2.02) by about 2 years (p &lt;0.005). ConclusionOur study indicated a longer period of independent walking for DMD patients living in high altitude areas. DMD boys might benefit by rehabilitation at higher altitude.

Antisense oligonucleotides (AOs) have demonstrated high potential as a therapy for treating genetic diseases like Duchene muscular dystrophy (DMD). As a synthetic nucleic acid, AOs can bind to a targeted messenger RNA (mRNA) and regulate splicing. AO-mediated exon skipping transforms out-of-frame mutations as seen in DMD into in-frame transcripts. This exon skipping approach results in the production of a shortened but still functional protein product as seen in the milder counterpart, Becker muscular dystrophy (BMD). Many potential AO drugs have advanced from laboratory experimentation to clinical trials with an increasing interest in this area. An accurate and efficient method for testing AO drug candidates in vitro, before implementation in clinical trials, is crucial to ensure proper assessment of efficacy. The type of cell model used to examine AO drugs in vitro establishes the foundation of the screening process and can significantly impact the results. Previous cell models used to screen for potential AO drug candidates, such as primary muscle cell lines, have limited proliferative and differentiation capacity, and express insufficient amounts of dystrophin. Recently developed immortalized DMD muscle cell lines effectively addressed this challenge allowing forthe accurate measurement of exon-skipping efficacy and dystrophin protein production. This chapter presents a procedure used to assess DMD exons 45-55 skipping efficiency and dystrophin protein production in immortalized DMD patient-derived muscle cells. Exons 45-55 skipping in the DMD gene is potentially applicable to 47% of patients. In addition, naturally occurring exons 45-55 in-frame deletion mutation is associated with an asymptomatic or remarkably mild phenotype as compared to shorter in-frame deletions within this region. As such, exons 45-55 skipping is a promising therapeutic approach to treat a wider group of DMD patients. The method presented here allows for improved examination of potential AO drugs beforeimplementation in clinical trials for DMD.

Objective Duchene Muscular dystrophy (DMD) is the common X-linked heterogenous progressive muscular dystrophy characterized by mutations in the DMD gene. The frequency of dystrophin gene mutations is varied in different DMD population. A precise diagnosis can help to reduce the severity of DMD since it aids in planning of targeted medical treatment and required therapies. This study was aimed to investigate the mutation type, their rate and distribution of DMD’S in southern India. Materials & Materials An observational study was conducted on 250 genetically confirmed DMD patients from March,2019 to March,2021. The distribution pattern and rate of mutations (deletion, duplication, nonsense mutations, minor mutations) were investigated. Results Mutation spectrum was studied on 250 DMD patients, of which 63% exon deletion pattern were reported. 16% deletions were detected in proximal hot region (exons 3-28). The duplications were found 21% in the proximal hotspot largest region (exon 3-25). 16% of the patients reported single deletion (45 exon), 10.7% reported deletions of exon 44. Point mutations detected in 6%, small mutations were detected in 1.2%, non-sense mutations were detected in 2% of study population respectively. Missense Mutations were detected in 0.8% of study population.Conclusion This study estimates mutation spectrum of exon deletion pattern (63%) was predominantly identified in distal region; duplication was most frequent in proximal region. Point mutations, Nonsense mutations and small mutations have a least accountability. This study adds a real world evidence for developing research therapies in DMD.

Duchene muscular dystrophy (DMD) is the most common muscular dystrophy inchildhood, affecting ∼1:5000 male live births worldwide. DMD is a geneticdisorder with X-linked recessive inheritance pattern characterized by a severemuscular phenotype with progressive muscle weakness and atrophy due topathogenic variations within the DMD gene. Two cases are reported to date in theliterature of individuals with a diagnosis of both DMD and West syndrome;neither of which had the degree of additional genetic abnormalities that ourpatient demonstrates. We present a male infant with West syndrome, and multiplepathogenic variants, the ominous one being in the DMD gene. This case adds toconfirming that West syndrome expands the spectrum of epilepsy that may bepresent in DMD patients. Additionally, this case can identify how the early useof steroids may shed light on effects of early symptomatic treatment of DMD.

Duchene and Becker Muscular Dystrophy (DMD/ BMD) are x-linked disorders that both are the result of heterogeneous mutations in the dystrophin gene. The frequency and distribution of dystrophin gene deletions in DMD/ BMD patients show different patterns among different populations. This study investigates the deletion rate, type, and distribution of this gene in the Azeri Turk population of North West Iran. In this study, 110 patients with DMD/ BMD were studied for intragenic deletions in 24 exons and promoter regions of dystrophin genes by using multiplex PCR. Deletions were detected in 63 (57.3%) patients, and around 83% localized in the mid-distal hotspot of the gene (on exons 44-52), 21 cases (33.3 %) with single-exon deletions, and 42 cases (66.6%) with multi-exonic deletions. The most frequent deleted exons were exon 50 (15 %) and exon 49 (14%). No deletion was detected in exon 3. This study suggests that the frequency and pattern of dystrophin gene deletions in DMD/ BMD in the Azeri Turk population of North West Iran occur in the same pattern when compared with other ethnic groups.

Background:Duchene muscular dystrophy (DMD) is a progressive muscular disorder. Cardiac disorder is the second-most common cause of death in children with DMD, with 10%–20% of them dying of cardiac failure. Heart rate variability (HRV) is shown to be a predictor of cardio-autonomic function. Physiotherapy (PT) is advised for these children as a regular treatment for maintaining their functional status. The effect of yogic practices on the cardio-autonomic functions has been demonstrated in various neurological conditions and may prove beneficial in DMD.Materials and Methods:In this study, 124 patients with DMD were randomized to PT alone or PT with yoga intervention. Home-based PT and yoga were advised. Adherence was serially assessed at a follow-up interval of 3 months. Error-free, electrocardiogram was recorded in all patients at rest in the supine position. HRV parameters were computed in time and frequency domains. HRV was recorded at baseline and at an interval of 3 months up to 1 year. Repeated-measures ANOVA was used to analyze longitudinal follow-up and least significant difference for post hoc analysis and P < 0.05 was considered statistically significant.Results:In our study, with PT protocol, standard deviation of NN, root of square mean of successive NN, total power, low frequency, high-frequency normalized units (HFnu), and sympathovagal balance improved at varying time points and the improvement lasted up for 6–9 months, whereas PT and yoga protocol showed an improvement in HFnu during the last 3 months of the study period and all the other parameters were stable up to 1 year. Thus, it is evident that both the groups improved cardiac functions in DMD. However, no significant difference was noted in the changes observed between the groups.Conclusion:The intense PT and PT with yoga, particularly home-based program, is indeed beneficial as a therapeutic strategy in DMD children to maintain and/or to sustain HRV in DMD.

Introduction:Duchene muscular dystrophy (DMD) is a neuromuscular disease of childhood, which has clear progression. The international standardized care guidelines for DMD suggest that palliative care is essential for the affected children.Objective:To explore the parent's understanding of palliative care services available for children with DMD and the challenges faced by them in utilizing the same.Methods:A cross-sectional qualitative exploratory study was conducted among six families of boys diagnosed with DMD. A semi-structured interview guide with prompts was used to conduct in-depth interviews which lasted for an average of 1 h. Thematic analysis was done to identify the pattern or themes.Results:The major themes identified were “palliative care, living with DMD, Awareness about palliative care services and challenges.” Awareness about palliative care services is the dominant theme identified as influencing rest of the experiences narrated by the parents of children with DMD.Discussion:Integration of palliative care services from an early stage of the illness can help the child to make transition from one stage to another stage of the illness. To ensure the utilization of the available palliative care services, there is a need to create awareness about it among the general public.Conclusion:Introducing the concept of palliation of symptoms and ensuring quality of life of the child with DMD by accessing the available services can aid the parents to reach out for help for their child.

Targeted next generation sequence analyses in a cohort of 961 previously described patients with clinically suspected Duchene muscular dystrophy (DMD) revealed that 145/961 (15%) had variants in genes associated with other muscular dystrophies (OMDs). NGS was carried out in DMD negative patients after deletion/duplication analysis followed by WES for No variant cases. The majority of patients with OMDs had autosomal recessive diseases that included Limb-Girdle Muscular Dystrophies (LGMDs), Bethlem, Ullrich congenital Myopathies and Emery-Driefuss muscular dystrophy. 3.5% of patients were identified with other disorders like Charcot-Marie Tooth and Nemaline myopathy. A small percentage of patients, 0.6% remain undiagnosed. Of a total of 78 genetic variants identified, 44 were found to be novel. Interestingly, a third of patients with OMDs were found to have LGMD2E/R4, a severe form of LGMD that afflicts young children with clinical symptoms similar to DMD. Almost one third of the unrelated LGMD2E/R4 patients had the same point mutation (c.544A>C) in the SGCB gene, suggestive of a founder effect, described here for the first time in India. This study underscores the need for a complete genetic work up to precisely diagnose patients and to initiate appropriate counseling programs, disease management and prevention strategies.

Introduction Cheyne-Stokes breathing (CSB) has rarely been identified in the pediatric population. Neuromuscular diseases (NMD) such as Duchene Muscular Dystrophy (DMD) can predispose patients to sleep-disordered breathing including central sleep apnea (CSA) and CSB. Sleep-disordered breathing in children with NMD may not have symptoms; thus, treatment can be delayed. Currently, there is limited data to support resolution of CSB in DMD with dilated cardiomyopathy post-transplant. Report of Cases: We present a 15-year old female with a significant history of both dilated cardiomyopathy and DMD who presented with acute on chronic heart failure. Due to her disease progression, she was listed for heart transplant. Prior to her transplant, she completed an inpatient polysomnography (PSG) to rule out sleep-disordered breathing due to concerns of snoring and dyspnea during sleep. Her Pediatric Daytime Sleepiness Scale score (PDSS) was 8. The polysomnogram recorded moderate obstructive sleep apnea (OSA) and central sleep apnea (CSA) consistent with Cheyne-Stokes breathing along with rare premature ventricular contractions (PVCs). Patient was started on BPAP of 13/8 cm H2O with a back-up rate of 12 breaths per minute after titration study. The patient subsequently received a heart transplant in which the patient’s dyspnea and snoring resolved. Post-transplant PSG pending to reassess the severity of sleep-disordered breathing. Conclusion Though CSA can be seen in children, CSB is rarely seen in children with either heart failure or muscular dystrophy. When CSB is observed, the cornerstone of treatment is correcting the underlying cause. This patient demonstrated CSB with symptoms that improved with BPAP and now post-heart transplant. When both heart failure and neuromuscular disease are involved, close monitoring for clinical symptoms along with screening for CSB is important and may affect overall quality of life and recovery. Support (If Any)

La distrofia muscular de Duchenne (DMD) es una distrofinopatía rápidamente progresiva con herencia ligada al cromosoma X. Este reporte describe el caso de una mujer con historia familiar de hermano y sobrinos con DMD, que acudió a consulta para orientación e información sobre riesgos inherentes a una eventual planificación familiar. Le propusimos participar en un programa piloto de asesoramiento genético para determinar su estado de portador o no de la variante causal de DMD en la familia. Esta primera experiencia ilustra la importancia de tener un programa de asesoramiento genético para el diagnóstico de portadores asintomáticos de enfermedades neurogenéticas en regiones con bajos recursos. Se incluyen reflexiones y comentarios sobre aspectos positivos y retos presentados durante el proceso, las políticas de apoyo presente y futuro para el afronte de los complejos problemas planteados por éste y similares diagnósticos.

Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy.

Effects of an Individualized Aquatic Therapy Program on Respiratory Muscle Function in Adolescents with Muscular Dystrophy

Electrocardiographic changes in cases of duchenne muscular dystrophy