Dysferlinopathies

Abstract

Dysferlin is a sarcolemmal protein that plays an important role in patching defects in skeletal membrane by regulating vesicle fusion with the sarcolemma. Mutations in the dysferlin gene can lead to a variety of clinical phenotypes. Affected individuals usually present with early involvement of the posterior calf muscles (Miyoshi myopathy) in their teens or early twenties, but can present with proximal greater than distal weakness similar to other limb-girdle muscular dystrophies (LGMD2B), with anterior tibial weakness, an axial myopathy (e.g., rigid spine syndrome or hyperkyphosis resembling bent spine syndrome), or any combination of the above. Muscle biopsies may be quite inflammatory, often resulting in a misdiagnosis as polymyositis. Unfortunately, there are no medical therapies available at this time.