Disease Directory Periodic Paralysis
Neuromuscular

Periodic Paralysis

Also known as: hyperkalemic periodic paralysis, hypokalemic periodic paralysis, HypoPP, HyperPP

Prevalence

1 in 100,000

Onset

Childhood to adolescence (first decade for HyperPP, second for HypoPP)

Type

Autosomal dominant

Gene

SCN4A, CACNA1S

About Periodic Paralysis

Periodic Paralysis encompasses a group of channelopathies causing episodic attacks of muscle weakness or paralysis associated with abnormal serum potassium levels. Hypokalemic Periodic Paralysis (HypoPP) is caused by mutations in CACNA1S or SCN4A and is triggered by high carbohydrate intake or rest after exercise; Hyperkalemic Periodic Paralysis (HyperPP) is caused by SCN4A gain-of-function variants and is triggered by fasting, cold, or potassium ingestion. Persistent interictal weakness develops in many patients over time.

Common Clinical Features

Episodic attacks of flaccid muscle weakness or paralysis lasting hours Attacks triggered by identifiable precipitants (food, exercise, cold, stress) Normal or near-normal strength between attacks early in disease Progressive interictal proximal muscle weakness in chronic disease Myotonia (in HyperPP with SCN4A mutations) Respiratory involvement during severe attacks Abnormal serum potassium during attacks (low in HypoPP, high in HyperPP)

Clinical Trial Eligibility Tips

What to know before applying to Periodic Paralysis trials.

Genetic subtype (HypoPP vs HyperPP and the causative gene) is required for most trials — potassium channel subtype (CACNA1S vs SCN4A) determines drug mechanism eligibility

Attack diary documentation including frequency, duration, potassium levels during attacks, and known triggers is essential and may form part of a run-in period in trial protocols

Exercise EMG (McManis protocol) and provocative testing results may be requested as objective diagnostic confirmation alongside genetic testing

Patient Resources

Patient Organization

Periodic Paralysis International

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Orphanet

European reference resource for rare diseases (ORPHA:681)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

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Find recruiting Periodic Paralysis trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Periodic Paralysis. Updated daily.

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