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Disease Profile

Dysferlinopathy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Categories

Musculoskeletal Diseases

Summary

Dysferlinopathies are a group of muscle diseases that have a slow progression of muscle weakness and atrophy (wasting). The diseases in the group are:[1][2] 

  • Miyoshi myopathy, where there is weakness and atrophy (wasting)of the muscles of the legs that are closer to  the feet (distal myopathy)
  • Limb-girdle muscular dystrophy type 2B (LGMD2B), where there is  weakness and atrophy of the muscles of the pelvic and shoulder
  • Scapuloperoneal syndrome, where weakness and atrophy affect both the distal legs and shoulder girdle muscles
  • Distal myopathy with anterior tibial onset, where there is weakness of the front part of the leg and foot drop
  • A form of congenital muscular dystrophy that was referred in a few people, and
  • A condition where there are not symptoms but only an elevated level of the muscular enzyme CK in the blood tests. 

All dysferlinopathies are caused by pathogenic variations (mutations) in the DYSF gene which result in a deficiency of the protein dysferlin (hence, the name), important for the efficient repair of muscle fibers. Inheritance is autosomal recessive. There is no cure or specific treatment. Management depend on the symptoms and is aimed to improve the quality of life and the life expectation. Research to find an effective treatment is ongoing.[3]

Symptoms

The symptoms associated with dysferlinopathies are highly variable.[2] Some patients have no symptoms, while others develop severe functional disability.[2] Miyoshi myopathy and limb-girdle muscular dystrophy type 2B are two common forms of dysferlinopathy. We have summarized symptoms of these conditions below.

In general, muscular dystrophies cause wasting and weakening of muscles. In limb-girdle muscular dystrophies the muscles in the shoulder and pelvic girdle (the large muscles around the top part of the arms and legs) are most affected.[4] Early symptoms of limb-girdle muscular dystrophies include difficulty with running, climbing stairs, standing, and walking.[5] As the disease progresses, it may become difficult for some patients to do activities that require the arms to be raised for a duration (e.g., combing hair).[5]

In Myoshi myopathy, early symptoms are most pronounced in the distal parts of the legs (i.e., the calf muscles). Patients experience weakness and atrophy in these muscles which may make it difficult for them to stand on tiptoe. As the disease progresses the muscle weakness and atrophy may spread to the thighs and gluteal muscles, forearms, and shoulder girdle muscles, which can result in additional symptoms including difficulty climbing stairs, standing, and walking, as well as a decrease in grip strength.[6]

Symptoms in both Myoshi myopathy and limb-girdle muscular dystrophy type 2B may affect one side more than the other.[6] While these conditions differ in the initial distribution of muscle involvement, as they progress there is little clinical difference between them.[7][2] There is no significant difference in the rate of progression between them and progression is typically slow.[7]

In a recent study of 40 patients with dysferlin gene mutations by Nguyen et al., 50% of the patients were diagnosed as having typical Miyoshi myopathy or Limb-girdle muscular dystrophy type 2B. Unusual phenotypes included a mixed phenotype, which the authors referred to as "proximodistal." Thirty-five percent of the patients had this phenotype and had a combination of distal and proximal onset. Two other phenotypes included a "pseudometabolic myopathy" and "asymptomatic hyperCKemia" which were found in 10% and 5% of the patients respectively.[2]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Dysferlinopathy. Click on the link to view a sample search on this topic.

            References

            1. Aoki M. Dysferlinopathy. GeneReviews. 2015; https://www.ncbi.nlm.nih.gov/books/NBK1303/.
            2. Nguyen K. Phenotypic study in 40 patients with dysferlin gene mutations: High frequency of atypical phenotypes. Arch Neurol. 2007;
            3. Begam M, Collier AF, Mueller AL, Roche R, Galen SS & Roche JA. Diltiazem improves contractile properties of skeletal muscle in dysferlin-deficient BLAJ mice, but does not reduce contraction-induced muscle damage. Physiological Reports. 2018; 6(11):e13727. https://www-ncbi-nlm-nih-gov.ezproxy.nihlibrary.nih.gov/pmc/articles/PMC5995314/.
            4. Bushby KMD, Straub V, Lochmuller H, Eagle M, Guglieri M, Hastings L. Limb girdle muscular dystrophy. Muscular Dystrophy Campaign. https://mdausa.org/disease/limb-girdle-muscular-dystrophy/overview. Accessed 2/18/2008.
            5. Limb-Girdle Muscular Dystropy. The Muscular Dystrophy Association. https://mda.org/disease/limb-girdle-muscular-dystrophy.
            6. Aoki M. Dysferlinopathy. GeneReviews. 2004; https://www.ncbi.nlm.nih.gov/books/NBK1303/. Accessed 2/18/2008.
            7. Ueyama H. et al. Clinical heterogeneity in dysferlinopathy. Internal Medicine. 2002;
            8. DYSF gene. Genetics Home Reference. 2014; https://ghr.nlm.nih.gov/gene/DYSF#resources.

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