Clinical Guidance
Dysferlinopathy includes a spectrum of muscle disease characterized by two major phenotypes (Miyoshi muscular dystrophy [MMD] and limb-girdle muscular dystrophy type 2B [LGMD2B]) and two minor phenotypes (asymptomatic hyperCKemia and distal myopathy with anterior tibial onset [DMAT]) . The major and minor phenotypes can occur within families having the same pathogenic variants [, , , , ]. The weakness and atrophy may be asymmetric with any of these presentations. Miyoshi muscular dystrophy. Young adults have muscle weakness and atrophy most marked in the distal part of the legs, especially the gastrocnemius and soleus muscles. Early on, affected individuals are not able to stand on tiptoe, but retain the ability to stand on the heels. Over a period of years, the weakness and atrophy spread to the thighs and gluteal muscles, at which time climbing stairs, standing, and walking become difficult. The forearms may become mildly atrophic with decrease in grip strength; the small muscles of the hands are spared. The weakness may eventually include the shoulder girdle muscles . Limb-girdle muscular dystrophy type 2B is characterized by early weakness and atrophy of the pelvic and shoulder girdle muscles that begins in adolescence or young adulthood, with slow progression. The spectrum of muscle involvement can also on occasion manifest as the scapuloperoneal syndrome with initial weakness of the shoulder girdle muscles combined with distal weakness of the legs or congenital muscular dystrophy with early onset – as observed, for example, in two sibs with hypotonia beginning between birth and age two months who had delayed motor development and serum CK concentrations that were normal or slightly elevated before age three years . Asymptomatic hyperCKemia. Some individuals have only a marked elevation of serum CK concentration. This is usually considered a presymptomatic presentation of myopathy in an individual who eventually develops muscle weakness and atrophy. Sometimes the calf muscles are enlarged; this presentation may be confused with a dystrophinopathy (i.e., Duchenne or Becker muscular dystrophy). Distal myopathy with anterior tibial onset is characterized by leg weakness that involves the muscles of the anterior compartment of the leg, causing foot drop . Table 2. Dysferlinopathy: Comparison of Phenotypes by Select Features
