diagnosis and screening for DMD

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder diagnosed in childhood. Limited newborn screening in the US often delays diagnosis. With multiple FDA-approved therapies, early diagnosis is crucial for timely treatment but may entail other benefits and harms. Using a community-based survey, we explored how parents of siblings with DMD perceived early diagnosis of one child due to a prior child's diagnosis. We assessed parents' viewpoints across domains including diagnostic journey, treatment initiatives, service access, preparedness, parenting, emotional impact, and caregiving experience...

OBJECTIVES: To evaluate the incidence rate of Duchenne muscular dystrophy (DMD) in the male newborns in the Ningxia region and establish a critical threshold for screening DMD in newborns to distinguish between the normal population and affected individuals. METHODS: A total of 10 000 male newborns were screened using immunofluorescence analysis of creatine kinase isoenzyme concentrations in heel spot dried blood specimens. Newborns with the concentrations higher than the critical threshold were recalled for serum creatine kinase measurements...

BACKGROUND: The rapidly evolving clinical landscape of Duchenne muscular dystrophy (DMD) is driving innovative approaches for early diagnosis through genomic newborn bloodspot screening (NBS). However, the potential impact of these programs on families and healthcare systems remains unexplored. This study assessed the perceived benefits, harms, barriers, and enablers for DMD NBS amongst primary caregivers of children with DMD and healthcare professionals (HCPs). METHODS: This Australian multi-centre cross-sectional study used a mixed-methods convergent methodology...

Reliable disease models are critical for medicine advancement. Here, we established a versatile human disease model system using patient derived extracellular vesicles (EVs), which transfer a pathology-inducing cargo from a patient to a recipient naïve model organism. As a proof of principle, we applied extracellular vesicles from serum of muscular dystrophy patients to C. elegans and demonstrated their capability to induce a spectrum of muscle pathologies including lifespan shortening and robust impairment of muscle organization and function...

BACKGROUND: To systematically evaluate the diagnostic accuracy of the creatine kinase isoenzyme-MM (CK-MM) test in newborn screening for Duchenne muscular dystrophy (DMD). METHODS: A comprehensive literature search was conducted up to October 31, 2022, in PubMed, Embase, Cochrane Library, Web of Science, and Scopus Database. To evaluate the diagnostic value, the sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and Q∗ index were pooled...

BACKGROUND: Duchene Muscular Disorder (DMD) is a severe X-linked recessive neuromuscular disease. Previous reports predicted that one-third of cases with a fatal X-linked recessive disease will be caused by a novel mutation, and the mutation rate for DMD seems to be higher in males. OBJECTIVE: A novel mutation in the DMD gene DMD (NM_004006.3):c.92A>G (p.Lys31Arg) is suggested for males because of their heterozygous mothers carrying the mutant alleles. METHOD: Whole Exome Sequencing (WES) was done for a 25-year-old female followed by the screening of the novel mutation in her parents and her brother by the Sanger sequencing technique...

OBJECTIVE: This report summarizes the key discussions from the "Early Care (0-3 years) in Duchenne Muscular Dystrophy" meeting, which aimed to address the challenges and opportunities in the diagnosis and care of Duchenne muscular dystrophy (DMD) and female carriers within the 0-3-year age group. METHODS: The meeting brought together experts and healthcare providers who shared insights, discussed advancements in DMD care, and identified research needs. Presentations covered diagnostic challenges, approved therapies, clinical trials, identification of young female carriers, and the importance of clinical care and support for families...

Although progress had been made in clarifying the pathogenesis of Duchenne muscular dystrophy (DMD), significant work needs to be done to unveil detailedly the cellular and molecular mechanisms associated with DMD for developing efficacious treatments. To identify the hub genes and dysregulated pathways in the progression of DMD, GSE13608, GSE38417 and GSE109178 mRNA microarray datasets were downloaded from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) between DMD and normal tissues were obtained, and function enrichment analyses were carried out...

Duchenne and Becker muscular dystrophies (DMD/BMD) are caused by complex mutations in the dystrophin gene ( DMD ). Currently, there is no integrative method for the precise detection of all potential DMD variants, a gap which we aimed to address using long-read sequencing. The captured long-read sequencing panel developed in this study was applied to 129 subjects, including 11 who had previously unsolved cases. The results showed that this method accurately detected DMD mutations, ranging from single-nucleotide variations to structural variations...

Despite the early onset of clinical signs suggestive of Duchenne muscular dystrophy (DMD), a diagnosis is often not made until four years of age or older, with a diagnostic delay of up to two years from the appearance of the first symptoms. As disease-modifying therapies for DMD become available that are ideally started early before irreversible muscle damage occurs, the importance of avoiding diagnostic delay increases. Shortening the time to a definite diagnosis in DMD allows timely genetic counseling and assessment of carrier status, initiation of multidisciplinary standard care, timely initiation of appropriate treatments, and precise genetic mutation characterization to assess suitability for access to drugs targeted at specific mutations while reducing the emotional and psychological family burden of the disease...

INTRODUCTION: Elevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia. METHODS: This multi-center, prospective study enrolled patients aged 3-216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months...

BACKGROUND: Drug repurposing could provide novel treatment options for Duchenne muscular dystrophy. Because tamoxifen-an oestrogen receptor regulator-reduced signs of muscular pathology in a Duchenne muscular dystrophy mouse model, we aimed to assess the safety and efficacy of tamoxifen in humans as an adjunct to corticosteroid therapy over a period of 48 weeks. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 12 study centres in seven European countries...

Clinicians specialized in the diagnosis and management of persons living with early-stage Alzheimer's disease need to enable access, for those meeting criteria, to the new class of disease modifying drugs (DMDs). These drugs act on amyloid β42 and delay progression of symptoms. Thus, there will be interest from patients and families. Over the short term, the use of antibodies administered intravenously with serial MRIs to detect amyloid-related imaging abnormalities (ARIA) may require participation in structured phase 4 studies or in registries with third party funding for support staff and MRI scans...

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis. METHODS: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD...

BACKGROUND: Preimplantation genetic testing (PGT) for monogenic disorders (PGT-M) for germline mosaicism was previously highly dependent on polymerase chain reaction (PCR)-based directed mutation detection combined with linkage analysis of short tandem repeats (STRs). However, the number of STRs is usually limited. In addition, designing suitable probes and optimizing the reaction conditions for multiplex PCR are time-consuming and laborious. Here, we evaluated the effectiveness of next generation sequencing (NGS)-based haplotype linkage analysis in PGT of germline mosaicism...

Duchenne's muscular dystrophy (DMD) is a debilitating X-linked recessive disorder of dystrophin gene expression that culminates in the downregulation of dystrophin in cardiac and skeletal muscle. As a result, there is progressive muscle weakness, fibrosis, and atrophy. The skeletal and cardiac muscle degeneration rapidly progresses to the respective loss of ambulation and death from cardiac muscle failure by the second and fourth decades of life. Although muscle degeneration has been demonstrated in utero patients are initially asymptomatic...

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity. To fill this critical gap, we present here novel data about dystrophin protein fragments detected in human plasma by a suspension bead immunoassay using two validated anti-dystrophin-specific antibodies...

Duchenne Muscular Dystrophy (DMD) is an X-linked inherited neuromuscular disorder caused by pathogenic variants in the dystrophin gene (DMD; locus Xp21.2). The variant spectrum of DMD is unique in that 65% of causative mutations are intragenic deletions, with intragenic duplications and point mutations (along with other sequence variants) accounting for 6% to 10% and 30% to 35%, respectively. The traditional strategy for molecular diagnostic testing for DMD involves initial screening for deletions/duplications using microarray-based comparative genomic hybridization followed by a full-sequence analysis of DMD for sequence variants...

BACKGROUND: Collagen VI-related myopathies with pathologic COL6A1, COL6A2, and COL6A3 variants manifest as a phenotypic continuum of rare disorders, including Bethlem myopathy (BM), characterized by early onset muscle weakness, proximal joint contractures, and distal joint laxity. Herein we discuss the concomitant orthopedic manifestations of BM, potential management strategies, and patient outcomes. METHODS: An IRB-approved retrospective cohort study (n=23) from 2 pediatric institutions with a confirmed diagnosis of BM...

BACKGROUND: Due to the broad application of next-generation sequencing, the molecular diagnosis of genetic disorders in pediatric neurology is no longer an unachievable goal. However, treatments for neurological genetic disorders in children remain primarily symptomatic. On the other hand, with the continuous evolution of therapeutic viral vectors, gene therapy is becoming a clinical reality. From this perspective, we wrote this review to illustrate the current state regarding viral-mediated gene therapy in childhood neurological disorders...