To report a case of late onset myopathy with heterozygous CACNA1S mutation.
CACNA1S mutations as dominant inheritance have been linked to susceptibility to malignant hyperthermia induced by volatile anesthetics and hypokalemic periodic paralysis often complicated by persistent muscle weakness following repeated episodes of weakness. Most recently, an early-onset congenital myopathy phenotype has also been described.
A 60-year-old gentleman with a past medical history of diabetes mellitus, and colon cancer with no recurrence presented with 2 year history of slowly progressive proximal arm and leg weakness without any oculo-bulbar symptoms. Family and social history were unremarkable as well as uneventful birth and developmental history. On neurological examination, there was bilateral symmetric proximal upper and lower limb weakness (MRC Grade 4- to 4+/5) as well as axial weakness but no sensory deficit and reflexes were preserved. Blood tests for acquired causes of muscle and neuromuscular junction diseases were negative. EMG revealed electrodiagnostic evidence of a proximal myopathic process with rare evidence of irritability. An upper limb muscle biopsy showed no active myopathic or inflammatory changes. Genetic testing revealed a likely pathogenic CACNA1S c.520C>T (p.Arg174Trp) mutation expected to disrupt its protein function. A long exercise test performed did not show significant decrement.
Our case, featuring a late-onset myopathy, expands the phenotype of CACNA1S related myopathy commonly characterized as congenital or early-onset hypotonia with progressive proximal and axial muscle weakness. Late onset genetic myopathy may pose significant diagnostic challenge. Patients can have milder symptoms and their muscle biopsies might lack typical histopathological features, potentially causing diagnostic delays. Hence, our case emphasizes the importance of genetic testing in appropriate clinical context. Additionally, our case contributes to understanding genotype-phenotype correlations, shedding light on the pathomechanisms of CACNA1S-related myopathy and potential treatment targets for future.