Periodic paralysis

Human genetic disease causing episodes of muscle weakness or paralysis

Periodic paralysis
Synonyms	Myoplegia paroxysmalis familiaris
Pronounce	N/A
Specialty	N/A
Symptoms	N/A
Complications	Respiratory failure, cardiac arrhythmia
Onset	Typically childhood or adolescence
Duration	Lifelong
Types	Hypokalemic periodic paralysis, Hyperkalemic periodic paralysis, Paramyotonia congenita, Andersen–Tawil syndrome
Causes	Genetic mutations affecting ion channels
Risks	Family history, exercise, carbohydrate-rich meals, stress
Diagnosis	Genetic testing, electromyography, blood tests for potassium
Differential diagnosis	Myasthenia gravis, thyrotoxic periodic paralysis, Guillain–Barré syndrome
Prevention	Avoidance of triggers (e.g. high-carb meals, strenuous activity)
Treatment	Lifestyle modification, potassium supplements, carbonic anhydrase inhibitors
Medication	Acetazolamide, dichlorphenamide, potassium chloride
Prognosis	Variable; symptoms may be controlled with appropriate management
Frequency	Rare
Deaths	Rare, may occur with severe cardiac involvement

Periodic paralysis is a group of rare genetic disorders characterized by recurring episodes of muscle weakness or paralysis. These episodes are often associated with abnormal levels of potassium in the blood, although some cases show normal potassium levels during attacks. Periodic paralysis is considered a form of channelopathy—a disorder caused by dysfunctional ion channels in muscle cell membranes.

Although primarily genetic, a similar condition known as thyrotoxic periodic paralysis may occur in individuals with hyperthyroidism, particularly in people of Asian or Latin American descent.

Types

Periodic paralysis disorders are typically inherited in an autosomal dominant fashion and can vary widely in expression and severity among individuals. The major forms include:

Hypokalemic periodic paralysis

• Caused by mutations in the CACNA1S or SCN4A gene.
• Episodes are triggered by a drop in blood potassium levels, often after exercise or high-carbohydrate meals.
• Common symptoms include weakness in the limbs, typically occurring upon waking or after rest.

Hyperkalemic periodic paralysis

• Caused by mutations in the SCN4A gene.
• Characterized by episodes triggered by elevated potassium levels or fasting.
• Muscle stiffness (myotonia) may accompany episodes, and attacks tend to be shorter than those of the hypokalemic form.

Paramyotonia congenita

• A related condition often co-occurring with hyperkalemic periodic paralysis.
• Characterized by muscle stiffness and weakness triggered by cold exposure or exercise.
• Unlike the other types, symptoms may worsen during activity.

Andersen–Tawil syndrome

• A rare and complex form of periodic paralysis caused by mutations in the KCNJ2 gene.
• Features include periodic paralysis, cardiac arrhythmias, and distinctive physical characteristics such as:
  • Scoliosis
  • Clinodactyly
  • Syndactyly
  • Micrognathia
  • Low-set ears
• Potassium levels can be low, high, or normal during episodes.
• Estimated to affect fewer than 100 individuals globally.

Signs and symptoms

Symptoms vary depending on the type but generally include:

• Sudden muscle weakness or paralysis lasting from minutes to hours
• Muscle stiffness or myotonia
• Triggering by rest after exercise, high-carb meals, cold exposure, or stress
• In some cases, difficulty breathing or heart rhythm abnormalities during severe attacks

Cause

Periodic paralysis is most often caused by mutations in genes that encode ion channels, especially those involving sodium (Na⁺), calcium (Ca²⁺), and potassium (K⁺) regulation:

• Mutations in the **SCN4A** gene affect sodium channels in skeletal muscle.
• Mutations in the **CACNA1S** gene affect calcium channels.
• Mutations in the **KCNJ2** gene affect potassium channels, as seen in Andersen–Tawil syndrome.

These mutations disrupt the normal flow of ions into and out of muscle cells, impairing their ability to contract and relax properly.

Triggers

Common triggers for periodic paralysis episodes include:

• Carbohydrate-rich meals
• Fasting
• Rest after strenuous exercise
• Emotional stress
• Cold temperatures
• Certain medications (e.g., glucocorticoids, beta-adrenergic agonists)

Diagnosis

Diagnosis is typically based on:

• **Clinical history** of episodic muscle weakness or paralysis
• **Serum potassium measurement** during an attack
• **Electromyography (EMG)** testing to assess muscle response
• **Genetic testing** to identify causative mutations
• **Provocative testing**, such as glucose-potassium challenge, may be used in specialized centers

Treatment

Management focuses on prevention and acute treatment of attacks:

Preventive measures

• Avoidance of triggers (e.g. certain foods, extreme temperatures)
• Low-carbohydrate diet
• Regular, moderate exercise

Medications

• **Potassium chloride** (oral or IV) for hypokalemic attacks
• **Carbonic anhydrase inhibitors** (e.g., acetazolamide, dichlorphenamide) may help reduce attack frequency
• **Beta-blockers** in some cases of thyrotoxic periodic paralysis

Acute management

• Careful administration of potassium (oral or IV) or glucose depending on potassium levels
• Close monitoring of cardiac and respiratory function during severe attacks

Prognosis

With appropriate management, many individuals can reduce the frequency and severity of attacks. However, in some cases, long-term muscle weakness (permanent myopathy) may develop. Patients with cardiac involvement, especially in Andersen–Tawil syndrome, require ongoing monitoring and treatment due to risk of serious arrhythmias.

See also

• Channelopathy
• Myopathy
• Thyrotoxic periodic paralysis
• Muscle weakness
• Andersen–Tawil syndrome
• Potassium

External links

• Periodic Paralysis – Genetic and Rare Diseases Information Center (GARD)
• Periodic Paralysis International