What is the definition of 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. 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. It is caused by variations (mutations) in the DYSF gene. Inheritance is autosomal recessive. Management may include physical therapy, use of mechanical aids, surgical intervention for orthopedic complications, respiratory aids, and social and emotional support.
Miyoshi myopathy is part of the group of diseases known as "Dysferlinopathies", which are caused by DYSF pathogenic variants.
What are the alternative names for Miyoshi Myopathy?
- Muscular dystrophy, distal, late onset, autosomal recessive
- Miyoshi distal myopathy
What are the causes for Miyoshi Myopathy?
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. 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".
What are the symptoms for Miyoshi Myopathy?
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:
- 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.
What are the current treatments for Miyoshi Myopathy?
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:.
- 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.
Is Miyoshi Myopathy an inherited disorder?
Miyoshi myopathy is inherited in an autosomal recessive manner. 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.