Dysferlinopathies are a spectrum of genetically inherited muscle disorders that result from deficiency of dysferlin protein. Dysferlinopathy includes two major phenotypes: Miyoshi muscular dystrophy and LGMD2B. Diagnosis is based on detection of DYSF gene mutations.

Upon further enquiry, patient reported frequent falls and clumsiness as a toddler with calf hypertrophy. She has always been slow in physical activities. A genetic myopathy was therefore suspected. Genetic testing revealed a heterozygous pathogenic mutation in DYSF gene, and another allele demonstrated variant of unknown significance (VUS). Due to the autosomal recessive inheritance of LGMD 2B, her muscle biopsy was sent for immunohistochemistry staining, which showed severely reduced to nearly absent dysferlin in isolation, confirming the diagnosis of LGMD 2B.

We emphasize that genetic myopathy should be considered in cases of “refractory myositis”. A comprehensive developmental history can guide clinicians towards early genetic testing. Performing immunochemistry on muscle biopsies can assist in clarifying VUS. Timely and accurate diagnosis can help prevent unnecessary immunomodulatory treatments in cases of genetic myopathy.