Dysferlinopathy is an autosomal recessive neuromuscular disorder caused by a deficiency of functional dysferlin protein due to mutations in the dysferlin gene. Dysferlinopathy is characterized by progressive muscle wasting and is most often clinically diagnosed as Limb-girdle muscular dystrophy type 2B (LGMD2B) or Miyoshi muscular dystrophy 1 (MMD1; a type of distal muscular dystrophy), depending on the initial pattern of muscle involvement at diagnosis. Dysferlinopathy is a rare disease, the exact incidence of which has not yet been determined.
Symptoms and Diagnosis
The symptoms of dysferlinopathy usually manifest in early adulthood between the ages of 16 and 25 and primarily affect the skeletal muscle of the limbs and the limb girdles (hips and shoulders), leaving critical muscles such as the heart and diaphragm largely unaffected. The majority of dysferlinopathy patients become non-ambulant within 10–20 years of diagnosis, but life expectancy is normal. There is a large amount of variability in the age of onset and progression of the disease.
Although LGMD2B and MMD1 are both caused by dysferlin deficiency, a diagnosis of LGMD2B is given when weakness initially presents in the proximal muscles (thighs and upper arms) while a diagnosis of MMD1 is given when weakness initially presents in the distal muscles (calves and lower arms). In both cases, weakness eventually progresses to include both distal and proximal muscles. Both LGMD2B and MMD1 are very difficult to diagnose, and patients are often misdiagnosed many times before they are successfully diagnosed with dysferlinopathy.
While "dysferlinopathy" simply refers to the absence of the dysferlin protein, LGMD2B and Miyoshi myopathy 1 are the confirmed diagnosis only when mutations in the dysferlin gene can be detected. It is essential that patients receive a genetic diagnosis for participation in clinical studies and trials specific to dysferlinopathy. The Jain Foundation is a non-profit family organization (www.jain-foundation.org) that helps patients with limb girdle muscular dystrophy to achieve a genetic diagnosis by organizing testing and covering the cost.