Abstract
Objective: To describe the baseline clinical and functional characteristics of an international cohort of 193 patients with dysferlinopathy.
Methods: The Clinical Outcome Study for dysferlinopathy (COS) is an international multicenter study of this disease, evaluating patients with genetically confirmed dysferlinopathy over 3 years. We present a cross-sectional analysis of 193 patients derived from their baseline clinical and functional assessments.
Results: There is a high degree of variability in disease onset, pattern of weakness, and rate of progression. No factor, such as mutation class, protein expression, or age at onset, accounted for this variability. Among patients with clinical diagnoses of Miyoshi myopathy or limb-girdle muscular dystrophy, clinical presentation and examination was not strikingly different. Respiratory impairment and cardiac dysfunction were observed in a minority of patients. A substantial delay in diagnosis was previously common but has been steadily reducing, suggesting increasing awareness of dysferlinopathies.
Conclusions: These findings highlight crucial issues to be addressed for both optimizing clinical care and planning therapeutic trials in dysferlinopathy. This ongoing longitudinal study will provide an opportunity to further understand patterns and variability in disease progression and form the basis for trial design.
GLOSSARY
- a-NSAA=
- adapted North Star Ambulatory Assessment;
- CK=
- creatine kinase;
- FVC=
- forced vital capacity;
- IB=
- immunoblot;
- IH=
- immunohistochemistry;
- LGMD=
- limb-girdle muscular dystrophy;
- LGMD2B=
- limb-girdle muscular dystrophy type 2B;
- ME=
- monocyte expression;
- MM=
- Miyoshi myopathy;
- MMT=
- Manual Muscle Testing;
- MRC=
- Medical Research Council;
- NSAA=
- North Star Ambulatory Assessment;
- OR=
- odds ratio;
- RFF=
- rise from floor;
- TUG=
- Timed Up and Go
Footnotes
Funding information and disclosures are provided at the end of the article. Go to Neurology.org/ng for full disclosure forms. The Article Processing Charge was paid by the University of Newcastle.
Coinvestigators are listed at Neurology.org/ng.
Supplemental data at Neurology.org/ng
- Received March 18, 2016.
- Accepted in final form June 16, 2016.
- © 2016 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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