Myofibrillar Myopathy Type 13 with Rimmed Vacuoles (HSPB8)

Myofibrillar Myopathy Type 13 with Rimmed Vacuoles (HSPB8) is an ultrarare, slowly progressive myofibrillar myopathy usually beginning in adolescence or adulthood with distal lower-limb weakness and atrophy, later involving proximal and truncal muscles. Muscle biopsy shows myofibrillar aggregates and rimmed vacuoles; axonal neuropathy may coexist.
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Genetics

Autosomal dominant disease caused by heterozygous pathogenic variants in HSPB8. The same gene can also cause distal hereditary motor neuropathy or CMT2L, reflecting an overlapping neuromuscular disease spectrum.

Molecular Mechanism

HSPB8 cooperates with BAG3, HSP70 and CHIP in chaperone-assisted selective autophagy. Pathogenic variants impair disposal of misfolded proteins and promote toxic aggregate accumulation, rimmed-vacuole formation and progressive failure of muscle and, in some patients, peripheral axons.

Therapy

No disease-modifying therapy is available. Management includes physiotherapy, orthoses and mobility support, with respiratory, cardiac and neuropathy surveillance guided by the individual phenotype. Autophagy modulation and allele-directed approaches are experimental.

CCP Activity

CCP performs comprehensive model characterization for preclinical development for HSPB8-associated MFM13.

Mouse Models Mouse Models & Gene Cards

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