Permanent muscle weakness in hypokalemic periodic paralysis

Area of Science:

• Neurology
• Genetics
• Muscle Diseases

Background:

• Hypokalemic periodic paralysis (HypoPP) is a rare genetic disorder.
• Mutations in the CACNA1S gene are a known cause of HypoPP.
• The full phenotypic spectrum of CACNA1S-related HypoPP is not well-defined.

Purpose of the Study:

• To comprehensively map the phenotypic spectrum in individuals with CACNA1S mutations causing HypoPP.
• To correlate clinical presentation with muscle imaging findings.

Main Methods:

• Retrospective analysis of 55 individuals with confirmed CACNA1S mutations.
• Data collection included medical history, muscle strength testing, and muscle MRI.
• Phenotypes were categorized based on clinical presentation.

Main Results:

• Phenotypes ranged from asymptomatic to classical periodic paralysis, mixed presentations, and permanent weakness.
• Muscle MRI showed fat replacement in all patients with permanent weakness and in a significant proportion of those without.
• Specific muscle groups like paraspinal, thigh, and calf muscles were most affected.
• Age correlated with increased weakness and fat replacement.

Conclusions:

• CACNA1S mutations lead to a diverse range of HypoPP phenotypes, including asymptomatic cases and fixed myopathy.
• Muscle MRI is valuable in assessing disease severity and detecting subclinical changes.
• Phenotypic variability exists even within families, and aging may contribute to a progressive myopathic component.