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A recessive distal myopathy characterized by weakness in the distal lower extremity posterior compartment (gastrocnemius and soleus muscles) and associated with difficulties in standing on tip toes.
ORPHA:45448Classification level: Disorder
Miyoshi myopathy (MM) is the most common form of recessive distal myopathy in populations with founder mutations such as Libyan and Israeli Jewish population, Italian and Spanish populations.
The typical age of onset of MM lies between 15 and 30 years (median 19 years) and the disease is characterized by muscle atrophy usually symmetric especially of the calf muscles (soleus and gastrocnemius). Onset in the anterior tibial muscles has been rarely reported. Ankle muscle stretch reflexes are lost and difficulties for toe walking or climbing stairs are encountered. Exercise-induced myalgia and aching discomfort in the calves can be an early symptom. Anterior compartment muscles of the distal lower extremities eventually become weak as well. As the disease progresses, patients will develop proximal leg and arm weakness to varying degrees. Decrease in respiratory functions have been reported only in few patients with moderate to severe disease. Bulbar or symptoms have not been reported.
MM is caused by mutations in the DYSF gene (2p13), which encodes dysferlin. The latter orchestrates skeletal muscle membrane repair and has also been associated with myogenesis, angiogenesis and microtubule dynamics.
Diagnosis of MM relies on laboratory findings showing an elevated serum creatine kinase level (20 to 150 times the normal), muscle biopsy routine reveals dystrophic features. Western blotting may help in cases with uncertain immunohistochemistry findings. Magnetic resonance imaging (MRI) of calf muscles show typical fatty replacement. EMG reveals 'myopathic' motor units and recruitment patterns. Diagnosis is confirmed by the genetic screening of DYSF.
Differential diagnosis includes autosomal recessive limb-girdle muscular dystrophy type 2L (LGMD2L), LGMD2B and qualitative or quantitative defects of caveolin-3.
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.
Management and treatment
No definitive treatments for MM exist and management is mainly supportive. To prolong survival and improve quality of life, weight control to avoid obesity, physical therapy and stretching exercises to promote mobility and use of mechanical aids to help ambulation and mobility are recommended.
Progression is variable with some patients remaining fairly stable with distal weakness, while others can have a more aggressive pattern involving both proximal and distal muscles. Patients may become wheelchair bound 10-30 years after onset of symptoms. Disease progression is usually related to disease duration rather than age of onset of symptoms.
- Clinical genetics review
- English (2015)