This patient’s presentation of normal physical development throughout life, followed by progressive motor decline with a predisposition to calves and proximal muscles, is most consistent with Limb-Girdle Muscular Dystrophy (LGMD). Indeed, there is some suggestion that many patients with LGMD may have increased athletic abilities compared to the general population prior to the start of the decline, as with our patient. This is a progressive disorder that often starts in the 2nd to 4th decades of life, and is hereditary in both autosomal dominant and recessive forms.
Given the decreasing cost, genetic testing is becoming more standard as an early and even first-line diagnostic test in patients with suspected LGMD. Hundreds of genes have been associated with LGMD, but the most common are associated with mutations in dysferlin (DYSF genes), dystroglycan (DAG1), sarcoglycan (SGC genes), and calpain (CAPN3). (Ref. 2)
The event of tachycardia, rigidity, and fever after surgery is consistent with anesthesia-induced malignant hyperthermia, which is often associated with ryanodine receptor (RYR) mutation. Indeed, about 5% of cases of LGMD are secondary to a mutation in the RYR1 gene. Our patient’s clinical presentation, therefore, is most consistent with this variant of LGMD as opposed to LGMD caused by calpain or other genes.
Ragged red fibers on muscle biopsy are most typically associated with mitochondrial disorders. On the contrary, most (~88%) of muscle biopsies in LGMD will show a myopathic picture with signs of active or past muscle necrosis and regeneration (Ref. 1). Ragged red fibers have been seen occasionally on LGMD biopsy (~4%), with about half of those patients having the dysferlinopathy variant of LGMD. Again, this would be much less likely, especially in a patient with likely RYR1-associated LGMD.
Anti-GAD65 can be seen in Stiff-person syndrome and Anti-SRP is seen in immune-mediated necrotizing myositis. These disorders do not fit the patient’s presentation as well.