Abstract
Background Limb girdle muscular dystrophies (LGMD) show phenotypic and genotypic variability. Autosomal recessive calpainopathies (LGMD R1) can mimic fascioscapulohumeral dystrophy (FSHD) and is an important differential in patients with a scapuloperoneal syndrome. Western blot can identify reduced calpain expression on muscle biopsy, but this may be secondarily decreased in muscular dystrophies other than LGMD R1. We describe a case of a patient with FSHD with reduced calpain expression on muscle biopsy.
Case description A 67-year-old male with a previous diagnosis of spinal muscular atrophy based on electromyography (EMG) findings and a prior muscle biopsy was seen in our clinic. His symptoms began with scapular winging at age 14, and gradually progressed to involve his lower extremities necessitating use of a wheelchair. Despite this, his neck and facial muscles were spared.
A comprehensive LGMD next generation sequencing (NGS) panel was performed. A heterozygous, pathogenic variant was identified in the calpain (CAPN3) gene. A muscle biopsy taken 12 years prior was re-examined showing features of a chronic dystrophic process, with reduced expression of calpain proteins on Western blot.
As the clinical phenotype was not consistent with an autosomal dominant calpainopathy, further genetic testing was undertaken. This revealed contraction of D4Z4 repeats with a permissive haplotype consistent with FSHD1.
Conclusion To our knowledge, this is the first case of a patient with FSHD that had reduced calpain expression on muscle biopsy. It remains uncertain if this is due to the heterozygous calpain mutation or if FSHD reduces calpain expression.
