Recurrent atraumatic compartment syndrome as a manifestation of genetic neuromuscular disease

Compartment syndrome (CS) is a medical emergency that occurs secondary to excessively high pressures within a confined fibro-osseous space, resulting in reduced perfusion and subsequent tissue injury. CS can be divided into acute forms, most commonly due to trauma and considered an orthopaedic emergency, and chronic forms, most commonly presenting in athletes with recurrent exercise-induced pain. Downstream pathophysiological mechanisms are complex but do share commonalities with mechanisms implicated in genetic neuromuscular disorders. Here we present 3 patients with recurrent CS in the context of a RYR1-related disorder (n = 1) and PYGM-related McArdle disease (n = 2), two of whom presented many years before the diagnosis of an underlying neuromuscular disorder was suspected. We also summarize the literature on previously published cases with CS in the context of a genetically confirmed neuromuscular disorder and outline how the calcium signalling alterations in RYR1-related disorders and the metabolic abnormalities in McArdle disease may feed into CS-causative mechanisms. These findings expand the phenotypical spectrum of RYR1-related disorders and McArdle disease; whilst most forms of recurrent CS will be sporadic, above and other genetic backgrounds ought to be considered in particular in patients where other suggestive clinical features are present.