Miyoshi myopathy

Alternate names

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

Definition

Miyoshi myopathy is a type of muscular dystrophy characterized by muscle weakness and atrophy (wasting), mainly in the distal parts of the legs.

Epidemiology

The exact prevalence of Miyoshi myopathy is unknown. In Japan, where the condition was first described, it is estimated to affect 1 in 440,000 individuals.

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.
• 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".

Inheritance

Autosomal recessive inheritance, a 25% chance

• Miyoshi myopathy is inherited in an autosomal recessive manner.
• which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
• 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.

Signs and 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:

• 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.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

30%-79% of people have these symptoms

• Adult onset(Symptoms begin in adulthood)
• Difficulty standing(Difficulty in standing)
• Difficulty walking(Difficulty in walking)
• Distal upper limb amyotrophy
• Exercise-induced myalgia(Exercise-induced muscle pain)
• Pelvic girdle muscle weakness
• Proximal amyotrophy(Wasting of muscles near the body)
• Quadriceps muscle weakness(Quadriceps weakness)
• Shoulder girdle muscle weakness(Weak shoulder muscles)
• Tibialis atrophy
• Tibialis muscle weakness

5%-29% of people have these symptoms

• Calf muscle hypertrophy(Increased size of calf muscles)
• Decreased/absent ankle reflexes
• Deposits immunoreactive to beta-amyloid protein
• Foot dorsiflexor weakness(Foot drop)
• Loss of ability to walk
• Toe walking(Toe-walking)
• Triceps weakness

Diagnosis

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

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.

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:

• 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.

NIH genetic and rare disease info

• NIH info on Miyoshi myopathy

Miyoshi myopathy is a rare disease.

Miyoshi myopathy Resources
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