Rare Oncology News

Disease Profile

Miyoshi myopathy

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.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adult

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ICD-10

G71.0

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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Other names (AKA)

Muscular dystrophy, distal, late onset, autosomal recessive; MM; Miyoshi distal myopathy

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

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.

Symptoms

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.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Adult onset
Symptoms begin in adulthood
0003581
Difficulty standing
Difficulty in standing
0003698
Difficulty walking
Difficulty in walking
0002355
Distal upper limb amyotrophy
0007149
Exercise-induced myalgia
Exercise-induced muscle pain
Muscle pain on exercise
Muscle pain with exercise
Muscle pain, exercise-induced

[ more ]

0003738
Pelvic girdle muscle weakness
0003749
Proximal amyotrophy
Wasting of muscles near the body
0007126
Quadriceps muscle weakness
Quadriceps weakness
0003731
Shoulder girdle muscle weakness
Weak shoulder muscles
0003547
Tibialis atrophy
0011399
Tibialis muscle weakness
0008963
5%-29% of people have these symptoms
Calf muscle hypertrophy
Increased size of calf muscles
0008981
Decreased/absent ankle reflexes
0200101
Deposits immunoreactive to beta-amyloid protein
0003791
Foot dorsiflexor weakness
Foot drop
0009027
Loss of ability to walk
0006957
Toe walking
Toe-walking
0040083
Triceps weakness
0031108
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Decreased Achilles reflex
0009072
Difficulty climbing stairs
Difficulty walking up stairs
0003551
Difficulty running
0009046
Distal amyotrophy
Distal muscle wasting
0003693
Distal muscle weakness
Weakness of outermost muscles
0002460
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

0003236
Lower limb muscle weakness
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs

[ more ]

0007340
Muscle fibrillation
0010546
Muscular dystrophy
0003560
Quadriceps muscle atrophy
Wasting of quad muscles
0009050
Variable expressivity
0003828

Cause

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]

Diagnosis

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

  • Midto 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]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • The Jain Foundation sponsors genetic testing to confirm the diagnosis of dysferlinopathy.

    Treatment

    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]

    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. 
            https://www.ncbi.nlm.nih.gov/omim/254130
            https://www.ncbi.nlm.nih.gov/omim/613318
            https://www.ncbi.nlm.nih.gov/omim/613319
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Miyoshi myopathy. 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. Miyoshi myopathy. Orphanet. 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=45448.
            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/.

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