Miyoshi myopathy

Miyoshi myopathy is a type of muscular dystrophy characterized by muscle weakness and atrophy (wasting), mainly in the distal parts of the legs.^[1] The first symptoms typically begin in young adulthood (on average 20 years of age) and include weakness and atrophy of the calves (sometimes asymmetrically), leading to inability to jump, run or walk on tiptoes. Over a period of years, the weakness and atrophy typically spread to the thighs and gluteal muscles. The forearms may become mildly atrophic with decrease in grip strength. Blood exams show an elevation of the creatine kinase (CK) often 10-100 times above the normal values.^[1] It is caused by variations (mutations) in the DYSF gene. Inheritance is autosomal recessive.^[2] Management may include physical therapy, use of mechanical aids, surgical intervention for orthopedic complications, respiratory aids, and social and emotional support.^[1]

Miyoshi myopathy is part of the group of diseases known as  "Dysferlinopathies", which are caused by DYSF pathogenic variants.

The disease have slow progression. Onset of signs and symptoms is typically in mid to late childhood or early-adulthood, (average age at onset of 19 years), and may include:^[1]

• Muscle weakness and atrophy (wasting), most marked in the distal parts of the legs, especially the gastrocnemius (calf) and soleus (Achilles tendon) muscles, specially in young adults
• Inability to stand on tiptoe, retaining the ability to stand on the heels
• Slow progression of weakness and atrophy spreading to the thighs and gluteal muscles, at which time climbing stairs, standing, and walking become difficult
• Mildly loss of muscular mass in  forearms with decrease in grip strength; the small muscles of the hands are not affected
• Weakness of the shoulder girdle muscles, which may occur on one side than the other.

Miyoshi myopathy is caused by pathogenic variants (mutations) in the DYSF gene, which encodes the dysferlin protein, a component of muscular fiber membranes. The presence and/or activity of the dysferlin protein is decreased or absent in individuals who have Miyoshi myopathy.^[2] This leads to abnormalities in the integrity of the muscle fiber membrane and problems with membrane repair. Mutations in the same gene are also involved in autosomal recessive limb-girdle muscular dystrophy type 2B (LGMD2B) and other diseases. The group of diseases caused by mutations in the DYSF gene are referred as "Dysferlinopathy".^[1]

Miyoshi myopathy is inherited in an autosomal recessive manner.^[1] Individuals have two copies of each gene (one copy inherited from each parent). In an individual affected with an autosomal recessive condition, both copies of the responsible gene have mutations. This means that each of the parents of an affected individual carry one mutated copy of the gene, and are therefore referred to as "carriers." Carriers of an autosomal recessive condition typically do not show signs or symptoms of the condition. When two carriers for the same condition have children together, each child has a 1 in 4 (25%) risk to have the condition, a 1 in 2 (50%) risk to be a carrier like each of the parents, and a 1 in 4 chance to not have the condition and not be a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.

Characteristics that may make the diagnosis of Miyoshi myopathy likely are:

• Mid- to late-childhood or early-adult onset of signs and symptoms
• Early and predominant involvement of the calf muscles
• Slow progression
• Elevation of serum creatine kinase (CK) concentration, often 10-100 times normal
• Primarily myogenic pattern on EMG (electromyography)
• Biopsy evidence of a chronic, active myopathy without rimmed vacuoles^[1]

Diagnosis typically depends on a combination of muscle biopsy and genetic testing. Muscle biopsy almost always indicates a primary dysferlinopathy (a disorder involving dysferlin, the protein absent or decreased in individuals with Miyoshi myopathy and limb-girdle muscular dystrophy type 2B). Molecular genetic testing of DYSF, the only gene associated with dysferlinopathy, is clinically available.^[1]

There is currently no cure or definitive treatment for Miyoshi myopathy. Management depend on the specific signs and symptoms, and is aimed to prolong survival and improve quality of life:.^[1]

• Physical therapy and stretching exercises to promote mobility and prevent contractures
• Use of mechanical aids such as canes, walkers, orthotics, and wheelchairs as needed to help ambulation and mobility
• Surgical intervention as needed for orthopedic complications such as foot deformity and scoliosis
• Use of respiratory aids when indicated
• Social and emotional support

Because  dysferlinopathies are progressive conditions, rehabilitative interventions should be focused on slowing down the of muscle weakness and wasting progression, rather than increasing muscle strength and walking capacity at the risk of causing irreversible muscle damage. Gene therapies are under investigation.^[3]

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

You can find relevant articles on Miyoshi myopathy through PubMed, a searchable database of biomedical journal articles. Although not all of the articles are available for free online, most articles listed in PubMed have a summary available. To obtain the full article, contact a medical/university library or your local library for interlibrary loan. You can also order articles online through the publisher’s Web site. Using "Miyoshi myopathy" as your search term should help you locate articles. Use the Limits or Advanced Search features to narrow your search results. Click here to perform a search.

The National Library of Medicine (NLM) Web site has a page for locating libraries in your area that can provide direct access to these journals (print or online). The Web page also describes how you can get these articles through interlibrary loan and Loansome Doc (an NLM document-ordering service). You can access this page at the following link: http://nnlm.gov/members/. You can also contact the NLM toll-free at 888-346-3656 to locate libraries in your area.

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. To find trials for individuals with Miyoshi myopathy, click on the link above and use "Miyoshi myopathy" as your search term. After you click on a study, review its "eligibility" criteria to determine its appropriateness. Use the study’s contact information to learn more. Check this site often for regular updates.

You can also contact the Patient Recruitment and Public Liaison (PRPL) Office at the National Institutes of Health (NIH). We recommend calling the toll-free number listed below to speak with a specialist, who can help you determine if you are eligible for any clinical trials. If you are located outside the United States, and would like to be contacted via telephone, you will need to provide your telephone number in full, including area code and international dialing prefix.
Patient Recruitment and Public Liaison Office
NIH Clinical Center
Bethesda, Maryland 20892-2655
Toll-free: 800-411-1222
Fax: 301-480-9793
Email: prpl@mail.cc.nih.gov
Web site: http://clinicalcenter.nih.gov/