Abstract Details

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.

To report a case of late onset myopathy with heterozygous CACNA1S mutation.

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.