Differentiation of Pediatric-Onset Duchenne and Becker Muscular Dystrophy Subphenotypes Using the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet)

2021 ◽  
pp. 1-8
Author(s):  
Jennifer G. Andrews ◽  
Molly Lamb ◽  
Kristin Conway ◽  
Natalie Street ◽  
Christina Westfield ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Disease Progression ◽  
Becker Muscular Dystrophy ◽  
Research Network ◽  
Anticipatory Guidance ◽  
Clinical Presentations ◽  
Study Results ◽  
Using Data ◽  
Pediatric Onset ◽  
Predict Disease Progression

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) phenotypes are used to describe disease progression in affected individuals. However, considerable heterogeneity has been observed across and within these two phenotypes, suggesting a spectrum of severity rather than distinct conditions. Characterizing the phenotypes and subphenotypes aids researchers in the design of clinical studies and clinicians in providing anticipatory guidance to affected individuals and their families. Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), we used K-means cluster analysis to group phenotypically similar males with pediatric-onset dystrophinopathy. We identified four dystrophinopathy clusters: Classical BMD, Classical DMD, late ambulatory DMD, and severe DMD. The clusters that we identified align with both ‘classical’ and ‘non-classical’ dystrophinopathy described in the literature. Individuals with dystrophinopathies have heterogenous clinical presentations that cluster into phenotypically similar groups. Use of clinically-derived phenotyping may provide a clearer understanding of disease trajectories, reduce variability in study results, and prevent exclusion of certain cohorts from analysis. Findings from studying subphenotypes may ultimately improve our ability to predict disease progression.

scholarly journals A Cross-Sectional Study of School Experiences of Boys with Duchenne and Becker Muscular Dystrophy

2016 ◽  
Vol 35 (2) ◽  
pp. 1-22 ◽  
Author(s):  
Aida Soim ◽  
Molly Lamb ◽  
Kimberly Campbell ◽  
Shree Pandya ◽  
Holly Peay ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Speech Therapy ◽  
Becker Muscular Dystrophy ◽  
Educational Interventions ◽  
Cross Sectional Study ◽  
Research Network ◽  
Sectional Study ◽  
Cross Sectional ◽  
Resource Room ◽  
Instructional Assistant

The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance, Tracking, and Research Network. Non-ambulatory males with Duchenne muscular dystrophy (DMD) were significantly more likely to use an instructional assistant and resource room support when compared to ambulant males with DMD at the time of the caregiver interview. Males with DMD who received occupational therapy were more likely to use an instructional assistant, while those who received speech therapy were more likely to repeat a grade, use an instructional assistant, and receive resource room support. Males with DMD whose primary caregivers had less than 12 years of education were more likely to use an instructional assistant and resource room support. Non-ambulatory males with DMD should continue receiving appropriate school accommodations so they can keep pace with their physical demands. Males with DMD with speech deficits should be considered for various educational interventions.

scholarly journals Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

2010 ◽  
Vol 1 (1) ◽  
pp. 8 ◽  
Author(s):  
Melinda F. Davis ◽  
Katalin H. Scherer ◽  
Timothy M. Miller ◽  
F. John Meaney
Keyword(s):  
Muscular Dystrophy ◽  
Medical History ◽  
Disease Progression ◽  
Disease Severity ◽  
Rating Scale ◽  
Becker Muscular Dystrophy ◽  
Assisted Ventilation ◽  
Structured Interviews ◽  
Course Of Disease ◽  
Outcome Indicators

Medical investigations use a wide variety of outcome indicators that are often not comparable. It can be challenging to integrate results across multiple studies that do not share a common metric. Some conditions such as Duchenne and Becker muscular dystrophy have a predictable course of disease progression. Severity can be inferred from a patient's medical history. This paper describes the development of a disease severity measure using common markers of disease progression. Rasch modeling was used to estimate severity using dichotomous events that indicate disease progression. Caregivers of 34 young men with Duchenne or Becker muscular dystrophy completed structured interviews about their care and medical history. Interview questions included surgeries (tendon release, scoliosis, tracheostomy), respiratory equipment (assisted ventilation, cough assist devices), and the use of other medical equipment (e.g., braces, walkers, wheelchairs, transfer boards, hospital beds). The resulting measure had a reliability of .83. The correlation between the severity measure and the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was .68. Preliminary results and item calibrations are provided for the severity measure that can be estimated from caregiver reports or administrative data. DOI:10.2458/azu_jmmss_v1i1_davis

scholarly journals Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

2010 ◽  
Vol 1 (1) ◽  
pp. 8
Author(s):  
Melinda F. Davis ◽  
Katalin H. Scherer ◽  
Timothy M. Miller ◽  
F. John Meaney
Keyword(s):  
Muscular Dystrophy ◽  
Medical History ◽  
Disease Progression ◽  
Disease Severity ◽  
Rating Scale ◽  
Becker Muscular Dystrophy ◽  
Assisted Ventilation ◽  
Structured Interviews ◽  
Course Of Disease ◽  
Outcome Indicators

Medical investigations use a wide variety of outcome indicators that are often not comparable. It can be challenging to integrate results across multiple studies that do not share a common metric. Some conditions such as Duchenne and Becker muscular dystrophy have a predictable course of disease progression. Severity can be inferred from a patient's medical history. This paper describes the development of a disease severity measure using common markers of disease progression. Rasch modeling was used to estimate severity using dichotomous events that indicate disease progression. Caregivers of 34 young men with Duchenne or Becker muscular dystrophy completed structured interviews about their care and medical history. Interview questions included surgeries (tendon release, scoliosis, tracheostomy), respiratory equipment (assisted ventilation, cough assist devices), and the use of other medical equipment (e.g., braces, walkers, wheelchairs, transfer boards, hospital beds). The resulting measure had a reliability of .83. The correlation between the severity measure and the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was .68. Preliminary results and item calibrations are provided for the severity measure that can be estimated from caregiver reports or administrative data. DOI:10.2458/azu_jmmss_v1i1_davis

scholarly journals Serum creatinine as a biomarker for dystrophinopathy: a cross-sectional and longitudinal study

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liang Wang ◽  
Min Xu ◽  
Dawei Liu ◽  
Yingyin Liang ◽  
Pinning Feng ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Muscular Dystrophy ◽  
Serum Creatinine ◽  
Disease Progression ◽  
Motor Function ◽  
Fatty Infiltration ◽  
Becker Muscular Dystrophy ◽  
Cross Sectional Study ◽  
Neuromuscular Disorder ◽  
Cross Sectional

Abstract Background Dystrophinopathy, a common neuromuscular disorder, includes Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Many researches are currently ongoing to develop curative approaches, which results in an urgent need for biomarkers of disease progression and treatment response. This study investigated whether the serum creatinine (SCRN) level can be used as a biomarker of disease progression in dystrophinopathy. Methods We enrolled 377 male patients with dystrophinopathy and 520 male non-dystrophinopathy controls in a cross-sectional study. From this cohort, 113 follow-up patients were enrolled in a longitudinal study. Patients’ demographic information, motor function, muscle fatty infiltration, and muscle dystrophin levels were evaluated. We investigated correlations between these parameters and SCRN levels, and determined changes in SCRN levels with maturation and with motor function changes. Results Our results showed SCRN levels correlated with motor function (FDR < 0.001) and timed test results (FDR between < 0.001–0.012), as well as with muscle fatty infiltration (FDR < 0.001) and dystrophin levels (FDR = 0.015 and 0.001). SCRN levels increased with maturation in control individuals; it slowly increased with maturation in patients with BMD but decreased generally with maturation in patients with DMD. The longitudinal study further demonstrated that SCRN levels were associated with motor function. Conclusions These findings indicated that the SCRN level is a promising biomarker for assessing disease progression in dystrophinopathy and could be used as a potential outcome measure in clinical trials.

scholarly journals Selection Approach to Identify the Optimal Biomarker Using Quantitative Muscle MRI and Functional Assessments in Becker Muscular Dystrophy

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012233
Author(s):  
Nienke M. van de Velde ◽  
Melissa T. Hooijmans ◽  
Aashley S.D. Sardjoe Mishre ◽  
Kevin R. Keene ◽  
Zaida Koeks ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Disease Progression ◽  
Intraclass Correlation ◽  
Becker Muscular Dystrophy ◽  
Knee Extension ◽  
Muscle Mri ◽  
Cross Sectional ◽  
Functional Assessments ◽  
The Difference ◽  
Muscle Groups

Objective:To identify the best quantitative fat-water MRI biomarker for disease progression of leg muscles in Becker muscular dystrophy (BMD) by applying a stepwise approach based on standardized response mean (SRM) over 24 months, correlations with baseline ambulatory tests and reproducibility.Methods:Dixon fat-water imaging was performed at baseline (n=24) and 24 months (n=20). Fat fractions (FF) were calculated for three center slices and the whole muscles for 19 muscles and six muscle groups. Contractile cross sectional area (cCSA) was obtained from the center slice. Functional assessments included knee extension and flexion force, and three ambulatory tests (North Star Ambulatory Assessment (NSAA), 10-meter run, six-minute walking test). MR parameters were selected using SRM (≥0.8) and correlation with all ambulatory tests (rho≤-0.8). Parameters were evaluated based on intraclass correlation coefficient (ICC) and standard deviation (SD) of the difference. Sample sizes (SS) were calculated assuming 50% reduction in disease progression over 24 months in a clinical trial with 1:1 randomization.Results:Median whole muscle FF increased between 0.2-2.6% without consistent cCSA changes. High SRMs and strong functional correlations were found for eight FF but no cCSA parameters. All parameters showed excellent ICC (≥0.999) and similar SD of the inter-rater difference. Whole thigh three center slices FF was the best biomarker (SRM=1.04, correlations rho≤-0.81, ICC=1.00, SD=0.23%, SS=59) based on low SD and acquisition and analysis time.Conclusion:In BMD, median FF of all muscles increased over 24 months. Whole thigh three center slices FF reduced the SS by approximately 40% compared to NSAA.

scholarly journals Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

2010 ◽  
Vol 1 (1) ◽  
pp. 8
Author(s):  
Melinda F. Davis ◽  
Katalin H. Scherer ◽  
Timothy M. Miller ◽  
F. John Meaney
Keyword(s):  
Muscular Dystrophy ◽  
Medical History ◽  
Disease Progression ◽  
Disease Severity ◽  
Rating Scale ◽  
Becker Muscular Dystrophy ◽  
Assisted Ventilation ◽  
Structured Interviews ◽  
Course Of Disease ◽  
Outcome Indicators

Medical investigations use a wide variety of outcome indicators that are often not comparable. It can be challenging to integrate results across multiple studies that do not share a common metric. Some conditions such as Duchenne and Becker muscular dystrophy have a predictable course of disease progression. Severity can be inferred from a patient's medical history. This paper describes the development of a disease severity measure using common markers of disease progression. Rasch modeling was used to estimate severity using dichotomous events that indicate disease progression. Caregivers of 34 young men with Duchenne or Becker muscular dystrophy completed structured interviews about their care and medical history. Interview questions included surgeries (tendon release, scoliosis, tracheostomy), respiratory equipment (assisted ventilation, cough assist devices), and the use of other medical equipment (e.g., braces, walkers, wheelchairs, transfer boards, hospital beds). The resulting measure had a reliability of .83. The correlation between the severity measure and the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was .68. Preliminary results and item calibrations are provided for the severity measure that can be estimated from caregiver reports or administrative data. DOI:10.2458/azu_jmmss_v1i1_davis

scholarly journals Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy

2017 ◽  
Vol 32 (7) ◽  
pp. 663-670 ◽  
Author(s):  
Rebecca Latimer ◽  
Natalie Street ◽  
Kristin Caspers Conway ◽  
Kathy James ◽  
Christopher Cunniff ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Clinical Care ◽  
Neuromuscular Disorders ◽  
Becker Muscular Dystrophy ◽  
Research Network ◽  
Multiple Systems ◽  
Secondary Conditions ◽  
Hyperactivity Disorder ◽  
Anxiety Depression ◽  
Mailed Survey

Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred nine caregivers of affected males (aged 3-31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The 5 most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones were found among nonambulatory males compared to ambulatory males. Attention-deficit hyperactivity disorder (ADHD) was more common in ambulatory than nonambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis.

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