Periodic paralysis.

ABSTRACT

Periodic paralysis is a rare, dominantly inherited disorder of skeletal muscle in which episodic attacks of weakness are caused by a transient impairment of fiber excitability. Attacks of weakness are often elicited by characteristic environmental triggers, which were the basis for clinically delineating subtypes of periodic paralysis and are an important distinction for optimal disease management. All forms of familial periodic paralysis are caused by mutations of ion channels, often selectively expressed in skeletal muscle, that destabilize the resting potential. The missense mutations usually alter channel function through gain-of-function changes rather than producing a complete loss-of-function null. The knowledge of which channel gene harbors a variant, whether that variant is expected to (or known to) alter function, and how altered function impairs fiber excitability aides in the interpretation of patient signs and symptoms, the interpretation of gene test results, and how to optimize therapeutic intervention for symptom management and improve quality of life.