diagnosis and screening for DMD

Duchenne/Becker muscular dystrophy (DMD/BMD) is the most common form of muscular dystrophy, accounting for over 50% of all cases. In this regard, in Russia we carry out a program of selective screening for DMD/BMD, which mainly involves male patients. The main inclusion criteria are an increase in the level of creatine phosphokinase (>2000 U/L) or an established clinical diagnosis. At the first stage of screening, patients are scanned for extended deletions and duplications in the DMD gene using multiplex ligase-dependent probe amplification (MLPA SALSA P034 and P035 DMD probemix, MRC-Holland)...

Advancements in therapies for Duchenne muscular dystrophy (DMD) have made diagnosis within the newborn period a high priority. We undertook a consortia approach to advance DMD newborn screening in the United States. This manuscript describes the formation of the Duchenne Newborn Screening Consortium, the development of the pilot protocols, data collection tools including parent surveys, and findings from the first year of a two-year pilot. The DMD pilot design is population-based recruitment of infants born in New York State...

Duchenne muscular dystrophy (DMD) is the most common pediatric-onset form of muscular dystrophy, occurring in 1 in 5,000 live male births. DMD is a multi-system disease resulting in muscle weakness with progressive deterioration of skeletal, heart, and smooth muscle, and learning disabilities. Pathogenic/likely pathogenic (P/LP) variants in the DMD gene, which encodes dystrophin protein, cause dystrophinopathy. All males with a P/LP variant in the X-linked DMD gene are expected to be affected. Two to 20% of female heterozygotes with a P/LP variant develop symptoms of dystrophinopathy ranging from mild muscle weakness to significant disability similar to Becker muscular dystrophy...

BACKGROUND: Xp21 contiguous gene deletion syndrome is a rare genetic metabolic disorder with poor prognosis in infants, involving deletions of one or more genes in Xp21. When deletions of adrenal hypoplasia (AHC), Duchenne muscular dystrophy (DMD), and chronic granulomatosis (CGD) loci are included, complex glycerol kinase deficiency (CGKD) can be diagnosed. We present a case of CGKD that was initially misdiagnosed and died during treatment in our hospital in terms of improving our understanding of the clinical features and diagnosis of this disease, as well as highlighting the need for more precise dosing of corticosteroid replacement therapy...

Duchenne muscular dystrophy is the most common form of muscular dystrophy diagnosed in childhood but is not routinely screened for prenatally or at birth in the United States. We sought to characterize the diagnostic experiences of families and describe their preferences for newborn screening (NBS). We conducted a registry-based survey of families with Duchenne and Becker muscular dystrophy that included open- and closed-ended questions regarding the journey to a diagnosis, preferences for when to learn of a diagnosis, and how knowledge of a diagnosis would impact life decisions...

Duchenne muscular dystrophy (DMD) is a progressive, fatal neuromuscular disorder typically diagnosed between 4 and 5 years of age. DMD currently has five FDA approved therapies, which has led to increased interest in newborn screening (NBS) for DMD. Our objective was to explore the perspectives and predicted practices of physicians (primarily neurologists) who will likely be responsible for the follow-up of infants identified with DMD through NBS. A short survey was developed and distributed to physicians who are responsible for providing care for patients with Duchenne at Certified Duchenne Care Centers across the USA...

OBJECTIVE: Large deletions and duplications account for 65%-80% of pathogenic Duchenne muscular dystrophy (DMD) variants. A nationwide carrier screening for DMD was initiated in Israel in 2020. We assessed the carrier rate and spectrum of variants detected in a cohort of women screened for DMD carrier status and analyzed screening efficacy and challenges related to DMD population screening. METHODS: A cohort of 12,362 women were tested at a single institute using multiplex ligation-dependent probe amplification based copy number analysis of the 79 DMD exons...

BACKGROUND: Duchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked muscular disease with an overall incidence of 1:5,000 live male births. Recent availability in treatment for DMD raised the need of early diagnosis, and DMD became as a selective item of newborn screening (NBS) since Feb. 2021 in our center. MATERIALS AND METHODS: Dried blood spots (DBS) muscle-type creatine kinase (CK) isoform was measured with a commercialized kit with age-adjusted cutoffs...

Early recognition of osteoporosis in children and adolescents is important in order to establish an appropriate diagnosis of the underlying condition and to initiate treatment if necessary. In this review, we present the diagnostic work-up, and its pitfalls, of pediatric patients suspected of osteoporosis including a careful collection of the medical and personal history, a complete physical examination, biochemical data, molecular genetics, and imaging techniques. The most recent and relevant literature has been reviewed to offer a broad overview on the topic...

INTRODUCTION/AIMS: Creatine kinase-MM (CK-MM) is a marker of skeletal muscle damage. Detection of elevated levels of CK-MM in newborns can enable an early suspicion of the diagnosis of Duchenne muscular dystrophy (DMD) prior to symptom onset. Our aim was to investigate CK-MM levels in DMD-affected and unaffected newborns using an immunoassay that measures CK-MM concentration in dried blood spots collected for routine newborn screening. METHODS: To validate the assay in our laboratory, CK-MM measurements and newborn demographic information were collected for 8,584 de-identified specimens and fifteen confirmed DMD patients...

In the Netherlands, the call to add 'non-treatable' disorders to the newborn bloodspot screening programme has found a sympathetic ear with the Government. In 2019, the Health Council of the Netherlands was formally asked for advice on the conditions under which bloodspot screening for such disorders might be offered. Here we present the reasoning and the recommendations of the resulting report, and briefly discuss its reception. The report holds on to the classical view that screening must benefit the child, but argues for a wider account of child benefit than only in terms of substantial health gains...

A pedigree genetic analysis of a female Duchenne muscular dystrophy (DMD) inherited from paternal chimerism was conducted to explore the genetic diagnosis strategy . No large deletions/duplications was found in the DMD gene of the proband. Next-generation sequencing (NGS) results showed that the proband had a heterozygous mutation in the DMD gene c.4707C>A (p.C1569X). This locus has not been reported in the literature and is considered as a pathogenic mutation. Sanger sequencing revealed that the father of the proband carried the same mutation, and the mosaic ratio was about 17...

Muscular Dystrophies (MDs) are a group of inherited diseases and heterogeneous in nature. To date, 40 different genes have been reported for the occurrence and/or progression of MDs. This study was conducted to demonstrate the application of next-generation sequencing (NGS) in developing a time-saving and cost-effective diagnostic method to detect single nucleotide variants (SNVs) and copy number variants (CNVs) in a single test. A total of 123 cases clinically suspected of MD were enrolled in this study. Amplicon panel-based diagnosis was carried out for 102 (DMD/BMD) cases and the results were further screened using multiplex ligation-dependent probe amplification (MLPA)...

BACKGROUND AND OBJECTIVES: Duchenne muscular dystrophy (DMD) is a paediatric neuromuscular disorder caused by mutations in the dystrophin gene. Geneotype-phenotype associations have been examined in glucocorticoid treated boys, but there are few data on the young glucocorticoid-naïve DMD population. A sample of young glucocorticoid-naïve DMD boys is described and genotype-phenotype associations are investigated. METHODS: Screening and baseline data were collected for all the participants in the Finding the Optimum Corticosteroid Regime for Duchenne Muscular Dystrophy (FOR-DMD)study, an international, multi-centre, randomized, double-blind, clinical trial comparing three glucocorticoid regimens in glucocorticoid-naïve, genetically confirmed boys with DMD between 4 and <8 years of age...

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD...

Duchenne muscular dystrophy (DMD) is not currently part of mandatory newborn screening, despite the availability of a test since 1975. In the absence of screening, a DMD diagnosis is often not established in patients until 3-6 years of age. During this time, irreversible muscle degeneration takes place, and clinicians agree that the earlier therapy is initiated, the better the long-term outcome. With recent availability of FDA-approved DMD therapies, interest has renewed for adoption by state public health programs, but such implementation is a multiyear process...

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD...

The major advances in genetic neuromuscular disorders in the last 30 years have been: (a) identification of the genetic basis for hundreds of these disorders, (b) through knowing the genes, understanding their pathobiology and (c) subsequent implementation of evidence-based treatments for some of the disorders. New genomic technologies are providing precision diagnosis, mode of inheritance and likely prognosis for more patients than ever before. Parents of children with a genetic diagnosis can then use preimplantation or prenatal diagnosis to avoid having further affected children if they wish...

INTRODUCTION/AIMS: Limb girdle muscular dystrophy type 2B (LGMDR2) and facioscapulohumeral muscular dystrophy (FSHD) are genetic muscular dystrophies with an increasing number of potential therapeutic approaches. The aim of this study is to report the data of exploratory digital outcomes extracted from wearable magneto-inertial sensors used in a non-controlled environment for ambulant patients with FSHD and LGMDR2 in a short-term, multicenter clinical study. METHODS: Digital outcomes (stride length, stride speed, and walk parameters in a non-controlled environment) were used as exploratory outcomes in the open-label study ATYR1940-C-004 in ambulant patients during the 3 mo of ATYR1940 treatment and 1 mo of follow-up...

INTRODUCTION/AIMS: Currently, there are no straightforward guidelines for the clinical and diagnostic management of hyperCKemia, a frequent and nonspecific presentation in muscle diseases. Therefore, we aimed to describe our diagnostic workflow for evaluating patients with this condition. METHODS: We selected 83 asymptomatic or minimally symptomatic patients with persistent hyperCKemia for participation in this Italian multicenter study. Patients with facial involvement and distal or congenital myopathies were excluded, as were patients with suspected inflammatory myopathies or predominant respiratory or cardiac involvement...