National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Dysferlinopathy

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]

 
Last updated: 7/2/2018
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]

Last updated: 7/12/2013
Dysferlinopathy is inherited in an autosomal recessive pattern.[6]
Last updated: 10/18/2013

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

In a previous series of patients with Miyoshi myopathy, 8 of 24 required a wheelchair after a 10-year-disease duration. This was similar to the findings of the Nguyen et al. study of 40 patients with dysferlinopathy. In addition Nguyen et al., observed few patients with a severe course of the disease. The most severe case they observed worsened over 5 years from a proximodistal onset to complete loss of ambulation, also with severe upper limb and axial weakness. The most mild case observed was of a 58-year-old man who was asymptomatic with isolated hyperCKemia.[2]

In the Nguyen et al. study, muscle inflammation, leading to a misdiagnosis of polymyositis, tended to correlate with a more severe course of disease, and they found that inflammation was most frequent in the patients with the proximodistal phenotype that they observed.[2]
Last updated: 7/12/2013

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Dysferlinopathy. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • The Muscular Dystrophy Association (MDA) is involved in the study of various forms of muscular dystrophy, including Dysferlinopathies. Click on the link to read more about the MDA's research interests.
  • The Muscular Dystrophy Campaign is involved in the research of muscular dystrophies, including dysferlinopathy.
  • The Jain Foundation provides information on clinical trials and research studies for dysferlinopathy.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Dysferlinopathy. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Dysferlinopathy:
    Dysferlin Registry
     

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

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.

News

Other Conferences

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I would like to know whether current research is finding ways to treat or cure this disease.What symptoms may people experience as their disease progresses? The likely progression of the disease may influence my decision to have more children. Are losing weight and a spine that is curving inward due to dysferlinopathy? Does dysferlinopathy affect the muscles of the face? Are patients able to feed themselves? See answer


  1. Aoki M. Dysferlinopathy. GeneReviews. 2015; http://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. http://mdausa.org/disease/limb-girdle-muscular-dystrophy/overview. Accessed 2/18/2008.
  5. Limb-Girdle Muscular Dystropy. The Muscular Dystrophy Association. http://mda.org/disease/limb-girdle-muscular-dystrophy.
  6. Aoki M. Dysferlinopathy. GeneReviews. 2004; http://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.