Reducing body myopathy (RBM) is a rare, X-linked myopathy attributed to mutations in the gene encoding for four and a half LIM domain protein 1 (FHL1) and is pathologically characterized by intracytoplasmic aggregates that reduce menadione nitro-blue-tetrazolium (NBT). Age of onset and clinical presentation varies widely with more severe forms presenting in infancy with rapidly progressive weakness and fatal respiratory insufficiency. Childhood and adult-onset forms can present with progressive proximal weakness, respiratory failure, rigid spine, cardiac involvement, and contractures.

A 45-year-old female with no significant medical history presented with 7 years of progressive, proximal weakness in all limbs. Her weakness started in her right arm followed by her left arm. Two years after symptom onset, she developed trouble climbing stairs and rising from a chair. She had no dysphagia, sensory, or bulbar symptoms. She had no significant family history. Creatinine kinase was elevated to 508 units of enzyme activity per liter. Neurologic examination was notable for proximal greater than distal limb weakness which was most pronounced in the deltoids, biceps, and triceps. She was hyporeflexic, had a waddling gait and winging of the left scapula. EMG was notable for myopathic units in proximal muscles. Muscle biopsy of the right quadriceps showed myopathic features, rare rimmed vacuoles and sarcoplasmic inclusions consisting of granular tubule-filamentous material compatible with reducing bodies. Genetic testing revealed a variant of uncertain significance identified in FHL1 (c.401A>C, p.Gln134Pro). This variant is not found in the literature or population databases, and is considered deleterious by multiple in silico models (VARITY, AlphaMissense, Revel).

This is the first reported case of RBM associated with the variant c.401A>C, p.Gln134Pro. With a wide spectrum of possible clinical presentations seen with RBM and FHL1 mutations, muscle biopsy remains a valuable diagnostic tool for genotype-phenotype correlation as newly identified variants are discovered.