Lower limb muscle strength impairment in late‐onset and adult myotonic dystrophy type 1 phenotypes

Petitclerc, Émilie; Hébert, Luc J.; Mathieu, Jean; Desrosiers, Johanne; Gagnon, Cynthia

doi:10.1002/mus.25451

Cited by 24 publications

(32 citation statements)

References 23 publications

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“…Values used during analysis were uncorrected for age, height, or sex, which were considered as independent variables in the multiple linear regression. Shoulder abductor, knee extensor and ankle dorsiflexor strength were measured twice for both left and right limbs, using a Microfet-2 (Hoggan Health Industries, USA), as previously described (40). The participant's position was standardized for each muscle group before measurement.…”

Section: Clinical Measurementsmentioning

confidence: 99%

Allele length of the DMPK CTG repeat is a predictor of progressive myotonic dystrophy type 1 phenotypes

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Légaré

Mathieu

et al. 2019

Human Molecular Genetics

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Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited disorder, caused by expansion of a germline and somatically unstable CTG repeat in the DMPK gene. Previously, CTG repeat length at birth has been correlated to patient age at symptom onset. Attempts to correlate CTG repeat length with progressive DM1 phenotypes, such as muscle power, have proven difficult. To better correlate genotype with progressive phenotypes, we have measured CTG repeat tract length and screened for interrupting variant repeats in 192 study participants from a well-characterized Canadian cohort. We have assessed genotype-phenotype correlations with nine progressive measures of skeletal muscle power and respiratory function. We have built statistical models which include confounding factors such as sex, age, height and weight to further explain variation in muscle power. Our analysis reveals a strong correlation between DM1 genotype and respiratory function and skeletal muscle power, as part of a complex model which includes additional modulators such as sex, age, height, weight, and the presence or absence of interrupting variant repeats. Distal skeletal muscle measurements, such as hand pinch and grip strength, show the strongest correlation with disease genotype. Detailed analysis of CTG repeat length, and incorporation of confounding factors, greatly improves the predictive ability of these models. They reveal a greater genetic influence on individual progressive phenotypes than on age at symptom onset, and for clinical trials will help optimise stratification and explain patient variability. They will also help practitioners prioritise assessment of the muscular power measurements which correlate best with disease severity.

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Section: Clinical Measurementsmentioning

confidence: 99%

Allele length of the DMPK CTG repeat is a predictor of progressive myotonic dystrophy type 1 phenotypes

Overend

Légaré

Mathieu

et al. 2019

Human Molecular Genetics

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“…Differences between adult‐onset and late‐onset phenotypes have been reported before . In addition, functional performance can differ due to age, gender, and body composition as reported not only in DM1 but also in healthy populations and other neurological disorder .…”

Section: Introductionmentioning

confidence: 61%

“…For example, after performing this model, walking tests (i.e., 6MWT and 10mWT) significance between male and female disappeared and the difference in 30SSS became significant highlighting the relevant influence of BMI and MIRS in these scores. The late‐onset phenotype subgroup differed significantly from the adult phenotype in all outcomes, which proves once more that generalizability of results should be cautious when considering data from mixed‐phenotypic samples and the association with muscular strength as measured by MIRS . However, using five categories of disease severity (i.e., MIRS) as compared to only two (i.e., Phenotype) was shown to be more strongly associated with patient performance.…”

Section: Discussionmentioning

confidence: 89%

Analysis of the functional capacity outcome measures for myotonic dystrophy

Jimenez-Moreno

Nikolenko

Kierkegaard

et al. 2019

Ann Clin Transl Neurol

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Objectives Defining clinically relevant outcome measures for myotonic dystrophy type 1 (DM1) that can be valid and feasible for different phenotypes has proven problematic. The Outcome Measures for Myotonic Dystrophy (OMMYD) group proposed a battery of functional outcomes: 6‐minute walk test, 30 seconds sit and stand test, timed 10 m walk test, timed 10 m walk/run test, and nine‐hole peg test. This, however, required a large‐scale investigation, Methods A cohort of 213 patients enrolled in the natural history study, PhenoDM1, was analyzed in cross‐sectional analysis and subsequently 98 patients were followed for longitudinal analysis. We aimed to assess: (1) feasibility and best practice; (2) intra‐session reliability; (3) validity; and (4) behavior over time, of these tests. Results OMMYD outcomes proved feasible as 96% of the participants completed at least one trial for all tests and more than half (n = 113) performed all three trials of each test. Body mass index and disease severity associate with functional capacity. There was a significant difference between the first and second trials of each test. There was a moderate to strong correlation between these functional outcomes and muscle strength, disease severity and patient‐reported outcomes. All outcomes after 1 year detected a change in functional capacity except the nine‐hole peg test. Conclusions These tests can be used as a battery of outcomes or independently based on the shown overlapping psychometric features and strong cross‐correlations. Due to the large and heterogeneous sample of this study, these results can serve as reference values for future studies.

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“…Adults with a genetically DNA-confirmed diagnosis of DM1 and presenting with the adult-onset or late-onset phenotype were recruited from the Saguenay Neuromuscular Clinic (Quebec, Canada). As part of a funded longitudinal study, 200 patients with DM1 were included at baseline (T1) (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) and were invited to attend a follow-up 9 years later (T2) (19)(20). At T2 59 of the 200 patients had died, 8 had left the region, 4 were excluded due to severe cognitive impairment, and 14 declined to participate (for personal reasons or lack of interest).…”

Section: Participantsmentioning

confidence: 99%

Responsiveness of performance-based outcome measures for mobility, balance, muscle strength and manual dexterity in adults with myotonic dystrophy type 1

Kierkegaard¹,

Petitclerc²,

Hébert³

et al. 2018

J Rehabil Med

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Lower limb muscle strength impairment in late‐onset and adult myotonic dystrophy type 1 phenotypes

Abstract: To avoid muscle wasting, physical activity recommendations should be made for the late-onset phenotype and in the early stages of the disease for the adult phenotype. MMT is not recommended for use in clinical trials. Muscle Nerve 56: 57-63, 2017.

Cited by 24 publications

References 23 publications

Allele length of the DMPK CTG repeat is a predictor of progressive myotonic dystrophy type 1 phenotypes

Allele length of the DMPK CTG repeat is a predictor of progressive myotonic dystrophy type 1 phenotypes

Analysis of the functional capacity outcome measures for myotonic dystrophy

Responsiveness of performance-based outcome measures for mobility, balance, muscle strength and manual dexterity in adults with myotonic dystrophy type 1

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