A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation

Objective: To determine the cause of sporadic rippling muscle disease (RMD) in a 24-year-old patient. Background: RMD is a rare myopathy characterized by percussion-induced rapid muscle contractions (PIRC), muscle mounding, and rippling waves. We have recently found that autosomal dominant RMD is caused by mutations in the caveolin-3 gene (CAV3) on chromosome 3p25. Possibly, increased activity of neuronal nitric oxide synthase (nNOS) contributes to the clinical characteristics of increased mechanical muscle hyperexcitability. Methods: Clinical examination, mutational analysis, and immunohistochemistry of muscle tissue were performed in a patient with sporadic RMD. Results: The authors observed a de novo CAV3 missense mutation Arg26Gln. Immunohistochemistry showed reduced caveolin-3 surface expression in a muscle biopsy. In addition, the authors found normal sarcolemmal nNOS expression and a reduced expression of alpha -dystroglycan in muscle fibers. Conclusions: These data confirm that RMD is caused by CAV3 mutations. Moreover, there is evidence that CAV3 mutations may also be found in patients without a positive family history of RMD.