Primary dysferlinopathies are a rare heterogeneous group of autosomal recessive muscular dystrophies that are caused by mutations in the exon gene. Although no specific therapies exist for dysferlinopathies, these disorders entail multiple pathways to muscle cell death, each of which is potentially a target for. The clinical phenotype of the dysferlinopathies is quite variable. Affected individuals usually present with early involvement of the posterior calf muscles ( Miyoshi.

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Other phenotypes are scapuloperoneal syndrome, distal myopathy with anterior tibial onset, elevated serum CK concentration only, and congenital muscular dystrophy.


Risk dysferli Family Members Parents of a proband The parents of an affected individual are obligate heterozygotes and therefore carry one DYSF pathogenic variant. Dysferlinopathies are inherited in an autosomal recessive pattern, being all the parents obligatory heterozygous.

Distal myopathy with anterior tibial onset. Inflammatory myopathy is sometimes misdiagnosed because inflammatory infiltrates are observed at the earlier stages of the disorder [ 13142628 – 30 ]. Therapies Under Investigation A double-blinded, placebo-controlled clinical trial of deflazacort in individuals with genetically confirmed dysferlinopathy has been completed [ Walter et al ].

pathiess The molecular analysis of the dysferlin gene confirms the diagnosis [ 13 ]. Patchy sarcolemmal and diffuse cytoplasmatic dysferlin Magnification 10X. Protein and gene analyses of dysferlinopathy in a large group of Japanese muscular dystrophy patients. Assessment of strength and dysferln in the arms, hands, legs, and feet; especially calf muscle. Because of variable and nonspecific patterns, immunoblot is generally considered the more reliable method for testing.


Dysferlinopathies represent a particular challenge to define natural history in order to plan relevant clinical trials.


Select your language of interest to view the total content in your interested language. Although there is not an overt cardiac involvement, there have been descriptions of affected patients that have cardiac impairment [ 43 – 45 ]. Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene s. Muscular dystrophy as well as generalized lipodystrophy in man and mice is due to its absence [ 8598 dysferlln, 99 ]. Hands or anterior lower leg.

The MGdeficient mice are not capable of resealing dysfetlin of the membrane [ 85]. Annual monitoring of muscle strength, joint range of motion, and respiratory function. Dysferlin mutations in Japanese Miyoshi myopathy: Other presentations include distal myopathy with anterior tibial onset initially distal muscle weakness that progressives to the proximal muscles and scapuloperoneal syndrome pathkes muscle weakness with weakness in the shoulder muscles.

The nonspecific sarcoplasmic alterations found can be focal disruption of myofilaments filled with mitochondria, rough endoplasmic reticulum, free ribosomes subsarcolemmally and streaming of Z line [ 14pthies61 ].

More detailed information for clinicians ordering genetic tests can pathiee found here. Proliferation of endomysial and perimysial connective tissue as well as loss of muscle fibers with fatty replacement and fibrosis at the advance stages can be found.

Miyoshi myopathy median age of onset 19 years is characterized by muscle weakness and atrophy, most marked in the distal parts of the legs, especially the gastrocnemius and soleus muscles.


dysfer,in Genomic organization of the dysferlin gene and novel dysferliin in Miyoshi myopathy. The flexor muscles gastrocnemius and soleus muscles are predominantly involved. When compared with other muscular dystrophies studied with the same methodology, it can be stated that in dysferlinopathies the percentage of the degenerating fibers is similar to that of sarcoglynopathies and lower than in Duchenne muscular dystrophy and myositis, but regarding regenerating fibers the percentage is higher than in sarcoglynopathies and lower than in Duchenne muscular dystrophy or myositis [ 29 ].


The diagnosis is made by the absence or reduced dysferlin in muscle by immunohistochemistry or immunoblotting [ 1332 ]. Monitoring for evidence of cardiomyopathy in those subtypes with known occurrence of cardiac involvement. Dysferlinopathies generally have a myopathic pattern.

The expression level of dysferlin protein can be either measured from blood monocytes [ 3334 ] or Western blot analysis.

Primary dysferlinopathies are a rare heterogeneous group of autosomal recessive muscular dystrophies that are caused by mutations in the exon gene encoding the protein dysferlin DYSF2p13, MIM [ 12 ]. Therefore, deflazacort treatment is not effective as a therapy for individuals with dysferlinopathies; additionally, the authors concluded that steroid treatment in general should be avoided in this condition [ Walter et al ].

Annual monitoring of muscle strength, joint range of motion, and respiratory function; and for evidence of cardiomyopathy for subtypes with cardiac involvement. Generally, the earlier symptoms begin, the faster they progress.