scholarly journals Is it the right time for an infant screening for Duchenne muscular dystrophy?

2020 ◽  
Vol 41 (7) ◽  
pp. 1677-1683
Author(s):  
Gian Luca Vita ◽  
Giuseppe Vita
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Best Practice ◽  
Screening Programme ◽  
Diagnostic Delay ◽  
Pilot Project ◽  
Small Population ◽  
New Drugs ◽  
Public Health Programme ◽  
Infant Screening

Abstract Newborn screening (NBS) is an essential, preventive public health programme for early identification of disorders whose early treatment can lead to significant reduction in morbidity and mortality. NBS for Duchenne muscular dystrophy (DMD) has been a controversial matter for many years, because of false positives, the lack of effective drugs and the need of more data about screening efficacy. The still high diagnostic delay of DMD and the current availability of drugs such as steroid, ataluren, eteplirsen, golodirsen and forthcoming new drugs, improving the clinical conditions if early started, make appropriate to begin a concrete discussion between stakeholders to identify best practice for DMD screening. A two-step system CK/DNA screening programme is presented to be performed in male infants aged between 6 months and 42 months involving more than 30,000 male infants. Five to eight DMD subjects are believed to be diagnosed. The pilot project would give the opportunity to test in a small population the feasibility of an infant screening programme, which in the near future could be applicable to an entire country.

scholarly journals Case Report: The Genetic Diagnosis of Duchenne Muscular Dystrophy in the Middle East

2021 ◽  
Vol 9 ◽  
Author(s):  
Fouad Alghamdi ◽  
Asmaa Al-Tawari ◽  
Hadil Alrohaif ◽  
Walaa Alshuaibi ◽  
Hicham Mansour ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Management ◽  
Best Practice ◽  
Middle Eastern ◽  
Genetic Diagnosis ◽  
Signs And Symptoms ◽  
Best Practice Guidelines ◽  
Related Quality

The timely and accurate genetic diagnosis of Duchenne muscular dystrophy (DMD) enables prompt initiation of disease management and genetic counseling and optimal patient care. Despite the existence of best practice guidelines for the diagnosis of DMD, implementation of these recommendations in different parts of the world is challenging. Here, we present 4 unique case studies which illustrate the different diagnostic pathways of patients with DMD in Middle Eastern countries and highlight region-specific challenges to achieving timely and accurate genetic diagnosis of DMD. A lack of disease awareness and consequential failure to recognize the signs and symptoms of DMD significantly contributed to the delayed diagnoses of these patients. Additional challenges included limited available funding for genetic testing and a lack of local specialist and genetic testing centers, causing patients and their families to travel vast distances for appointments in some countries. Earlier and more accurate genetic diagnosis of DMD in this region would allow patients to benefit from effective disease management, leading to improvements in health-related quality of life.

Diagnostic delay of rare diseases in Europe and in Hungary

2012 ◽  
Vol 153 (30) ◽  
pp. 1185-1190 ◽  
Author(s):  
Anett Földvári ◽  
Ildikó Szy ◽  
János Sándor ◽  
Gábor Pogány ◽  
György Kosztolányi
Keyword(s):  
Cystic Fibrosis ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Tuberous Sclerosis ◽  
Rare Diseases ◽  
Diagnostic Delay ◽  
Patient Organizations ◽  
Qualitative Survey ◽  
Centralized Care ◽  
Patients Experience

The long diagnostic delay is a characteristic problem of rare disease patients. Aims: Diagnostic delay was studied in 14 countries by EurordisCare2 involving patient organizations. Methods: 252 Hungarian patients (cystic fibrosis; Duchenne muscular dystrophy; tuberous sclerosis, retinitis pigmentosa, and Williams’ syndrome) completed the questionnaires. Results: The median delay was longer in Hungary than in Europe (cystic fibrosis: 227 vs. 45 days; Duchenne muscular dystrophy: 467 vs. 360 days; tuberous sclerosis: 155 vs. 120 days). Patients’ experience was similar in Hungary and in Europe. The proportion of misdiagnosis was 30.8% in Hungary (Europe: 41%), 34.8% of patients got diagnosis outside of living place region (EU: 26%) and 19.9% of them found the personal expenses too high (EU: 10%). Delivery of the diagnosis was unnecessary according to 27.4% of Hungarian patients (EU: 35%). Conclusions: The qualitative survey demonstrated that the problems with the diagnosis of rare diseases are widespread, the identified areas require interventions, and it confirmed the importance of centralized care. Orv. Hetil., 2012, 153, 1185–1190.

scholarly journals Implications of diagnostic delay in Duchenne muscular dystrophy.

BMJ ◽  
1983 ◽  
Vol 287 (6399) ◽  
pp. 1106-1107 ◽  
Author(s):  
T O'Brien ◽  
J R Sibert ◽  
P S Harper
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Diagnostic Delay

scholarly journals Teaching an Old Molecule New Tricks: Drug Repositioning for Duchenne Muscular Dystrophy

2019 ◽  
Vol 20 (23) ◽  
pp. 6053 ◽  
Author(s):  
Vitiello ◽  
Tibaudo ◽  
Pegoraro ◽  
Bello ◽  
Canton
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
State Of The Art ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Biological Molecules ◽  
New Drugs ◽  
Dystrophin Deficiency ◽  
Pass Through ◽  
Pathogenic Effects

: Duchenne muscular dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophies. The disease is caused by the lack of dystrophin, a structurally essential protein; hence, a definitive cure would necessarily have to pass through some form of gene and/or cell therapy. Cell- and genetic-based therapeutics for DMD have been explored since the 1990s and recently, two of the latter have been approved for clinical use, but their efficacy is still very low. In parallel, there have been great ongoing efforts aimed at targeting the downstream pathogenic effects of dystrophin deficiency using classical pharmacological approaches, with synthetic or biological molecules. However, as it is always the case with rare diseases, R&D costs for new drugs can represent a major hurdle for researchers and patients alike. This problem can be greatly alleviated by experimenting the use of molecules that had originally been developed for different conditions, a process known as drug repurposing or drug repositioning. In this review, we will describe the state of the art of such an approach for DMD, both in the context of clinical trials and pre-clinical studies.

Newborn screening pilot study in time of pandemic: Duchenne Muscular Dystrophy pilot project experience

2021 ◽  
Vol 132 ◽  
pp. S359
Author(s):  
Dorota Gruber ◽  
Wendy Chung ◽  
Julia Wynn ◽  
Lorraine Verdade ◽  
David Tegay ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Pilot Study ◽  
Muscular Dystrophy ◽  
Newborn Screening ◽  
Pilot Project

scholarly journals Prediagnosis pathway benchmarking audit in patients with Duchenne muscular dystrophy

2021 ◽  
pp. archdischild-2020-321451
Author(s):  
Vasantha Lakshmi Gowda ◽  
Miguel Fernandez ◽  
Manish Prasad ◽  
Anne-Marie Childs ◽  
Imelda Hughes ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Diagnostic Delay ◽  
Unmet Need ◽  
Definitive Diagnosis ◽  
Service Improvement ◽  
Time To Diagnosis ◽  
The Uk ◽  
Mean Time ◽  
Non Motor Symptoms

ObjectiveTo describe age and time at key stages in the Duchenne muscular dystrophy (DMD) prediagnosis pathway at selected centres to identify opportunities for service improvement.DesignA multicentre retrospective national audit.SettingNine tertiary neuromuscular centres across the UK and Ireland. A prior single-centre UK audit of 20 patients with no DMD family history provided benchmark criteria.PatientsPatients with a definitive diagnosis of DMD documented within 3 years prior to December 2018 (n=122).Main outcome measuresMean age (months) at four key stages in the DMD diagnostic pathway and mean time (months) of presentational and diagnostic delay, and time from first reported symptoms to definitive diagnosis. Type of symptoms was also recorded.ResultsOverall, mean age at definitive diagnosis, age at first engagement with healthcare professional (HCP) and age at first reported symptoms were 53.9±29.7, 49.9±28.9 and 36.4±26.8 months, respectively. The presentational delay and time to diagnosis were 21.1 (±21.1) and 4.6 (±7.9) months, respectively. The mean time from first reported symptoms to definitive diagnosis was 24.2±20.9. The percentages of patients with motor and/or non-motor symptoms recorded were 88% (n=106/121) and 47% (n=57/121), respectively.ConclusionsMajority of data mirrored the benchmark audit. However, while the time to diagnosis was shorter, a presentational delay was observed. Failure to recognise early symptoms of DMD could be a contributing factor and represents an unmet need in the diagnosis pathway. Methods determining how to improve this need to be explored.

Clinical and Genetic Characteristics in Young, Glucocorticoid-Naive Boys With Duchenne Muscular Dystrophy

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013122
Author(s):  
Marianela Schiava ◽  
Rachel Amos ◽  
Henriette VanRuiten ◽  
Michael P McDermott ◽  
Williams B Martens ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Stop Codon ◽  
Incidental Finding ◽  
Diagnostic Delay ◽  
Genetic Diagnosis ◽  
Neuromuscular Disorder ◽  
Double Blind ◽  
Genetic Characteristics ◽  
The Mean

Background and ObjectivesDuchenne 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.MethodsScreening 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.ResultsOne hundred and ninety-six boys were recruited. The meanage at randomization (+ standard deviation) was 5.8+ 1.0 years. The predominant mutation type was out of frame deletions 67.4%, (130/193) of which 68.5% (89/130) were amenable to exon skipping. The most frequent mutations were deletions amenable to exon 51 skipping 13.0% (25/193). Stop codon mutations accounted for 10.4% (20/193).The mean age at first parental concerns was 29.8 + 18.7 months, the mean age at genetic diagnosis was 53.9 + 21.9 months and the mean diagnostic delay was 25.9 + 18.2 months. The mean diagnostic delay for boys diagnosed following an incidental finding of isolated hyperCKemia (n=19) was 6.4 + 7.4 months. The mean ages at independent walking and talking in sentences were 17.1 + 4.2 and 29.0 + 10.7 months, respectively. Median height percentiles were below the 25th percentile regardless of age group. No genotype-phenotype associations were identified expect for boys with an exon 8 skippable deletions who had better performance on time to walk/run 10 meters (p=0.02)compared to boys with deletions not amenable to skipping.DiscussionThis study describes clinical and genetic characteristics of a sample of young glucocorticoid-naïve boys with DMD. A low threshold for CK testing can lead to an earlier diagnosis. Motor and speech delay were common presenting symptoms.The effects of low, pre-treatment height on growth and adults height requires further study. These findings may promote earlier recognition of DMD and inform study design for future clinical trials.

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