BAG3 myofibrillar myopathy presenting with cardiomyopathy

Area of Science:

• Neurology
• Genetics
• Cardiology

Background:

• Myofibrillar myopathies (MFMs) are a group of neuromuscular disorders characterized by myofibrillar dissolution.
• Mutations in the BCL2-associated athanogene 3 (BAG3) gene typically cause severe childhood-onset MFMs, involving weakness, cardiomyopathy, neuropathy, and early lethality.

Observation:

• This report details the first case of BAG3-related MFM where severe cardiomyopathy and cardiac transplantation at age eight preceded neuromuscular weakness by four years (onset at age 12).
• The patient presented with distal weakness and a severe sensorimotor neuropathy, confirmed by nerve biopsy showing axonal damage with secondary demyelination/remyelination.
• Muscle biopsy revealed extensive neuropathic changes, complicating the assessment of myopathic features.

Findings:

• A pathogenic p.Pro209Leu mutation in exon 3 of the BAG3 gene was identified, consistent with previous reports.
• This case demonstrates a distinct temporal progression of symptoms in BAG3-related MFM, with cardiac issues manifesting years before significant neuromuscular decline.

Implications:

• This case underscores the critical need to consider MFMs in pediatric patients presenting with a combination of cardiomyopathy and neuromuscular weakness.
• Early diagnosis and genetic testing for BAG3 mutations are crucial for managing this severe condition and providing appropriate genetic counseling.