To underscore the occurrence of a limb-girdle phenotype in HSPB8-related vacuolar myopathy. 

Heat shock protein B8 is a small heat shock protein that plays a key role in preventing protein aggregation and facilitating turnover of damaged proteins in mechanically-strained tissues. To date, very few pathogenic variants have been identified in HSPB8. These were initially discovered in inherited neuropathies and, more recently, in rare myopathies with myofibrillar and rimmed vacuolar pathology. Most reported HSPB8-related myopathy patients presented with distal weakness. 

We reviewed the clinical, laboratory and histological features of a patient with HSBB8-related myopathy presenting with proximal weakness.

A 23-year-old Caucasian man presented with a 4-year history of progressive proximal leg weakness with severe involvement of the iliopsoas and quadriceps muscles. He also had mild scapular winging, a contracture limiting neck flexion and increased lumbar lordosis. Electromyography revealed fibrillation potentials and myopathic findings most prominent in proximal and axial muscles, with intermixed long-duration motor unit potentials in a few proximal and distal muscles. Nerve conduction studies were normal. The creatine kinase level was mildly elevated. The electrocardiogram, echocardiogram and pulmonary function tests were normal. A biopsy of the quadriceps showed many fibres harbouring rimmed vacuoles. A few fibres displayed focal aggregates of myotilin and desmin, or punctate T-cell intracellular antigen 1 reactivity. Whole-exome sequencing identified a novel de novo heterozygous duplication in the last exon of HSPB8 (c.577_580dupGTCA, p.Thr194Serfs*23), which is absent from the gnomAD database.

HSPB8-related disorders can present with early onset limb-girdle myopathy without associated neuropathy. Sequencing of HSPB8 should be considered in the molecular evaluation of patients presenting with limb-girdle muscular dystrophy.