Severe phenotypes of paralysis periodica paramyotonia are associated with the Met1592Val mutation in the voltage-gated sodium channel gene (SCN4A) in a Chinese family.

Paralysis periodica paramyotonia (PPP) is caused by mutation of the adult skeletal muscle sodium channel gene's alpha (α)-subunit (SCN4A). Here, we report four generations of a Chinese family affected by a remarkably severe form of PPP with progressive myopathy. Routine electromyograms (EMG) showed myotonic discharge and after a long exercise test, compound motor action potential amplitudes were markedly decreased by 40-55%. Muscle biopsy revealed obvious vacuolar changes. Moreover, genetic analysis revealed the Met1592Val mutation in the α-subunit, SCN4A. The patients showed a striking clinical and electrophysiological improvement during treatment with acetazolamide. Thus, our findings showed that mutation of Met1592Val in the SCN4A gene is associated with aggressive development of PPP characterized by severe vacuolar myopathy.