2024 American Academy of Neurology Abstract Website

Objective:

We describe a unique case of 21-year-old woman with proximal more than distal lower extremity weakness who was initially treated as refractory autoimmune myositis, and later was confirmed to have limb-girdle muscular dystrophy type 2B (LGMD2B)

Background:

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.

Design/Methods:

Upon retrospective chart review, patient’s symptoms started 2 years ago after an uneventful vaginal delivery. She experienced proximal muscle weakness in bilateral lower extremities that progressed to distal muscle weakness in next few months. Her initial workup revealed elevated creatinine kinase of 17,962 with normal TSH/T4, and negative autoimmune antibodies, including myositis panel, anti SRP and HMG COA reductase antibodies. Her electrodiagnostic testing demonstrated myopathy with membrane irritability and MRI of bilateral thighs suggested muscle edema with fatty infiltration. Despite inconclusive muscle biopsy for inflammatory myositis, she was treated with steroids and IVIG for seronegative myositis without clinical improvement

Results:

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.

Conclusions:

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.