We report on a case of a 14-year-old boy with a novel c.347G>C variant (p.Arg116Pro) in HSPB3 presenting with congenital myopathy. HSPB3 has been related to an adult-onset distal hereditary motor neuromyopathy.

The proband presented a delay in motor milestones achievement and a history of frequent falls and early fatigability, which worsened slowly over time. Physical examination revealed a mildly hypomimic facies and slight weakness of the shoulder girdle. There was a severe right-convex rotoscoliosis with a right rib hump. There were no signs or symptoms of hypoventilation. EKG and echocardiogram were normal. His cognitive profile was fully in the norm. Creatine kinase values were normal. Muscle biopsy showed a myopathic pattern (predominance of Type I fibers and minicores). Muscle MRI showed an initial fatty infiltration of subscapularis and a widespread fatty infiltration in the lower limbs, with preserved muscle volumes.

Genetic sequencing revealed a novel heterozygous missense variant of the HSBP3 gene, segregated from the proband’s father. A skin biopsy was obtained to generate fibroblasts and start functional confirmation experiments, which are currently ongoing.

The father is also symptomatic, reporting the onset of symptoms from young adult age but has no limitation in the activities of daily life. His MRI showed a similar picture together with a severe involvement of the paravertebral muscles.

To our knowledge, this is the first report describing in the detail a case of congenital myopathy associated with HSPB3 mutations.