Dysferlinopathy: spectrum of pathological changes in skeletal muscle tissue

Dysferlinopathy is an autosomal recessive-limb girdle muscular dystrophy (AR-LGMD) caused due to the defect in gene encoding dysferlin, a sarcolemmal protein. Awareness of the variants and their relative frequency is essential for accurate diagnosis.

To study the spectrum of morphologic changes in immunohistochemically proven cases of dysferlinopathies, to correlate the findings with clinical phenotype and durations of illness and determine the frequency.

Dysferlinopathies seen over a period of 2 years at a tertiary neurological center were analyzed.

Clinically, majority had Miyoshi phenotype (46.6%) with distal involvement and LGMD phenotype (40%) with proximal muscle involvement. In addition, a proximo-distal and tibial muscle phenotype was encountered. Morphologically, rimmed vacuoles were noted in the Miyoshi phenotype. The presence of ragged red fibers, lobulated fibers and inflammation had no preference to a particular phenotype. Significant atrophy and lobulated fibers were noted in patients with longer duration of illness.

Dysferlinopathy was the second most common identifiable cause (21%) of LGMD next to sarcoglycanopathies (27%).