Abstract
Objectives Myofibrillary myopathies (MFM) are a heterogenous group of disorders characterised by myofibrillar dissolution and accumulation of protein degradation products in myofibres. BCL2-associated anthanogene 3 (BAG3)-related MFM has been reported to present with sensorimotor neuropathy and cardiomyopathy. We report a case of a 54-year-old man with a progressive sensorimotor axonal neuropathy with respiratory involvement who was found to have a novel BAG3 variant.
Case A 54-year-old man presented with a six-month history of increasing dyspnoea with severe restrictive ventilatory dysfunction evident on pulmonary function testing. He has a five-year history of progressive sensorimotor disturbance in his limbs with muscle cramps and gait impairment leaving him wheelchair-bound. Examination revealed marked wasting and florid fasciculations in the upper and lower limbs, distal greater than proximal weakness, absent reflexes and a stocking-and-glove distribution sensory disturbance. Electrodiagnostic studies confirmed a severe length-dependent sensorimotor axonal neuropathy with active and chronic denervation on electromyography. Singleton whole exome sequencing identified a heterozygous missense variant of unknown significance in BAG3 [NM_004281.3:c.625C>G, p.(Pro209Ala)]. Other variants in BAG3 at the same amino acid residue [p.(Pro209Leu) and p.(Pro209Gln)] have been reported to be associated with BAG3-related MFM. Subsequent muscle biopsy demonstrated chronic denervation and reinnervation of myofibres with pseudodystrophic changes, suggestive of an underlying myofibrillar myopathy. He was managed supportively with nocturnal bilevel positive airway pressure and discharged into supported accommodation.
Conclusion This is a case of adult-onset myofibrillary myopathy suspected to be due to a novel missense BAG3 variant located in a previously reported BAG3 mutation hotspot (Proline 209).
