Condition 101 About Dysferlinopathy

What is the definition of Dysferlinopathy?

Dysferlinopathies are a group of muscle diseases that have a slow progression of muscle weakness and atrophy (wasting).  The diseases in the group are: 
  • Miyoshi myopathy, where there is weakness and atrophy (wasting)of the muscles of the legs that are closer to  the feet (distal myopathy)
  • Limb-girdle muscular dystrophy type 2B (LGMD2B), where there is  weakness and atrophy of the muscles of the pelvic and shoulder
  • Scapuloperoneal syndrome, where weakness and atrophy affect both the distal legs and shoulder girdle muscles
  • Distal myopathy with anterior tibial onset, where there is weakness of the front part of the leg and foot drop
  • A form of congenital muscular dystrophy that was referred in a few people, and
  • A condition where there are not symptoms but only an elevated level of the muscular enzyme CK in the blood tests. 
All dysferlinopathies are caused by pathogenic variations (mutations) in the  DYSF gene which result in a deficiency of the  protein dysferlin (hence, the name),  important for the efficient repair of muscle fibers. Inheritance is autosomal recessive. There is no cure or specific treatment. Management depend on the symptoms and is aimed to improve the quality of life and the life expectation. Research to find an effective treatment is ongoing.


What are the symptoms for Dysferlinopathy?

The symptoms associated with dysferlinopathies are highly variable. Some patients have no symptoms, while others develop severe functional disability. Miyoshi myopathy and limb-girdle muscular dystrophy type 2B are two common forms of dysferlinopathy. We have summarized symptoms of these conditions below.

In general, muscular dystrophies cause wasting and weakening of muscles. In limb-girdle muscular dystrophies the muscles in the shoulder and pelvic girdle (the large muscles around the top part of the arms and legs) are most affected. Early symptoms of limb-girdle muscular dystrophies include difficulty with running, climbing stairs, standing, and walking. As the disease progresses, it may become difficult for some patients to do activities that require the arms to be raised for a duration (e.g., combing hair).

In Myoshi myopathy, early symptoms are most pronounced in the distal parts of the legs (i.e., the calf muscles). Patients experience weakness and atrophy in these muscles which may make it difficult for them to stand on tiptoe. As the disease progresses the muscle weakness and atrophy may spread to the thighs and gluteal muscles, forearms, and shoulder girdle muscles, which can result in additional symptoms including difficulty climbing stairs, standing, and walking, as well as a decrease in grip strength.

Symptoms in both Myoshi myopathy and limb-girdle muscular dystrophy type 2B may affect one side more than the other. While these conditions differ in the initial distribution of muscle involvement, as they progress there is little clinical difference between them. There is no significant difference in the rate of progression between them and progression is typically slow.

In a recent study of 40 patients with dysferlin gene mutations by Nguyen et al., 50% of the patients were diagnosed as having typical Miyoshi myopathy or Limb-girdle muscular dystrophy type 2B. Unusual phenotypes included a mixed phenotype, which the authors referred to as "proximodistal." Thirty-five percent of the patients had this phenotype and had a combination of distal and proximal onset. Two other phenotypes included a "pseudometabolic myopathy" and "asymptomatic hyperCKemia" which were found in 10% and 5% of the patients respectively.

What is the outlook (prognosis) for Dysferlinopathy?

In a previous series of patients with Miyoshi myopathy, 8 of 24 required a wheelchair after a 10-year-disease duration. This was similar to the findings of the Nguyen et al. study of 40 patients with dysferlinopathy. In addition Nguyen et al., observed few patients with a severe course of the disease. The most severe case they observed worsened over 5 years from a proximodistal onset to complete loss of ambulation, also with severe upper limb and axial weakness. The most mild case observed was of a 58-year-old man who was asymptomatic with isolated hyperCKemia.

In the Nguyen et al. study, muscle inflammation, leading to a misdiagnosis of polymyositis, tended to correlate with a more severe course of disease, and they found that inflammation was most frequent in the patients with the proximodistal phenotype that they observed.

Is Dysferlinopathy an inherited disorder?

Dysferlinopathy is inherited in an autosomal recessive pattern.

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