Periodic Paralyses (Hyperkalemic, Hypokalemic, Andersen-Tawil Syndrome)

Periodic Paralyses (Hyperkalemic, Hypokalemic, Andersen-Tawil Syndrome)

What is periodic paralysis?

Periodic paralysis (PP) refers to a group of rare inherited muscle disorders characterized by episodes of temporary muscle weakness or paralysis. These episodes occur because muscle cells become temporarily unable to respond normally to nerve signals. Symptoms typically begin in childhood or adolescence and may progress over time to persistent muscle weakness between attacks.

Episodes can range from mild weakness affecting specific muscle groups to severe generalized paralysis lasting hours or, in some cases, days. Common triggers include rest after exercise, carbohydrate-rich meals, fasting, stress, illness, cold exposure, alcohol consumption, and changes in blood potassium levels.

Periodic paralysis is most often caused by genetic variants affecting ion channels that regulate the movement of sodium, calcium, or potassium in muscle cells. The major forms of PP are classified by changes in blood potassium levels during attacks and by their underlying genetic cause. When a disease-associated genetic variant is not identified, a diagnosis of PP may be supported by detecting a reduction of muscle electrical activity after exercise (CMAP long exercise test).

Hyperkalemic periodic paralysis

What is hyperkalemic periodic paralysis (hyperPP)?

Hyperkalemic periodic paralysis (hyperPP) is a rare inherited muscle disorder caused by abnormalities in ion channels, the proteins that help regulate electrical signals in muscle cells. It is characterized by recurrent episodes of muscle weakness or paralysis that are often associated with elevated blood potassium levels during attacks. Some individuals may have normal potassium levels during episodes.

What are the symptoms of hyperPP?

Symptoms typically begin in childhood, often before age 10. Attacks usually last from 15 minutes to several hours, although longer episodes can occur.

Symptoms may include:

• Episodes of muscle weakness or paralysis
• Weakness that often affects the arms and legs
• Muscle stiffness (myotonia) between attacks
• Muscle cramps or heaviness
• Fatigue

Over time, many individuals develop permanent muscle weakness, and some may experience a chronic progressive myopathy that can affect mobility and daily activities.

Common triggers include:

• Rest after vigorous exercise
• Potassium-rich foods
• Fasting
• Cold exposure
• Emotional stress
• Pregnancy

Attacks often occur in the morning or after periods of inactivity.

What causes hyperPP?

HyperPP is caused by variants in the SCN4A gene, which provides instructions for a sodium channel involved in muscle function. These genetic changes alter how sodium channels work, making muscle fibers more susceptible to becoming electrically inactive and temporarily unable to contract normally.

HyperPP is usually inherited in an autosomal dominant pattern, meaning a person only needs to inherit one altered copy of the gene to develop the condition.

What is the progression of hyperPP?

HyperKPP has its onset in childhood. Unlike the case for most myopathies, some people with hyperKPP experience progressive, permanent muscle damage that occurs independently of the attacks. The frequency of attacks declines after middle age. Men and women are affected equally.

What is the status of research on hyperPP?

Research is focused on understanding how sodium channel dysfunction leads to muscle weakness and identifying treatments that can prevent attacks and reduce long-term muscle damage. Investigators are also studying gene-based therapies and improved outcome measures for future clinical trials.

Hypokalemic periodic paralysis

What is hypokalemic periodic paralysis (hypoPP)?

Hypokalemic periodic paralysis (hypoPP) is the most common form of periodic paralysis. It is characterized by episodes of muscle weakness or paralysis associated with low blood potassium levels during attacks.

What are the symptoms of hypoPP?

Symptoms often begin in late childhood or adolescence, although onset can occur at any age.

Symptoms may include:

• Transient episodes of muscle weakness or paralysis
• Weakness that typically affects the shoulders, hips, arms, and legs
• Episodes lasting several hours to several days
• Difficulty standing, walking, or lifting objects during attacks
• Progressive muscle weakness developing over time

Attack frequency varies widely. Some individuals experience only a few episodes during their lifetime, while others may have frequent attacks.

Common triggers include:

• High-carbohydrate meals
• Rest after strenuous exercise
• Alcohol consumption
• Emotional stress
• Illness

What causes hypoPP?

HypoPP is most commonly caused by variants in either the CACNA1S gene, which encodes a calcium channel, or the SCN4A gene, which encodes a sodium channel. These genetic changes make muscle fibers vulnerable to becoming electrically inactive when potassium levels fall.

HypoPP is usually inherited in an autosomal dominant pattern.

What is the progression of hypoPP?

In HypoPP, attacks usually begin in late childhood or the teenage years. Many individuals experience a slowly progressive myopathy, leading to permanent weakness in the legs and hips after about age 50. While women may have very mild or even no episodes of transient weakness, men and women are equally at risk for developing late onset permanent weakness.

What is the status of research on hypoPP?

Researchers continue to investigate the mechanisms underlying muscle weakness and permanent muscle damage in hypoPP. Current studies include natural history research, improved diagnostic tools, improved symptom management using drugs to support normal excitability of muscle, and gene-editing approaches aimed at correcting disease-causing genetic variants.

Andersen-Tawil syndrome

What is Andersen-Tawil syndrome?

Andersen-Tawil syndrome (ATS) is a rare form of periodic paralysis that affects skeletal muscle, the heart, and bone structure. It is distinguished from other forms of periodic paralysis by the presence of cardiac rhythm abnormalities and characteristic physical features.

ATS was first described by Danish physician Ellen Andersen in 1971 and later further characterized by neurologist Rabi Tawil and colleagues.

What are the symptoms of Andersen-Tawil syndrome?

The classic features of ATS include:

• Transeint episodes of muscle weakness or paralysis
• Cardiac arrhythmias (abnormal heart rhythms)
• Distinctive skeletal and facial features

Episodes of weakness may last from hours to days and can occur with low, high, or normal potassium levels.

Cardiac symptoms may include:

• Palpitations
• Irregular heartbeat
• Fainting (syncope)
• Ventricular arrhythmias

Physical features can include:

• Low-set ears
• Wide-set eyes
• Small lower jaw
• Curved fifth fingers (clinodactyly)
• Short stature
• Scoliosis

Not all individuals experience all three characteristic features, and variations may occur for affected individuals in the same family.

What causes Andersen-Tawil syndrome?

Most cases are caused by variants in the KCNJ2 gene, which encodes a potassium channel important for normal electrical activity in skeletal and cardiac muscle cells. Defects in this channel can impair muscle function and disrupt normal heart rhythm.

ATS is usually inherited in an autosomal dominant pattern.

What is the progression of Andersen-Tawil syndrome?

This disease has its onset in childhood or adolescence, and many individuals experience slowly progressive muscle weakness over time. Cardiac arrhythmias may occur in some, but serious cardiac events are uncommon. Permanent weakness may occur with age. Men and women are affected equally.

What is the status of research in Andersen-Tawil syndrome?

Current research is focused on understanding how potassium channel dysfunction affects skeletal muscle and heart function, identifying additional disease-causing genes, improving diagnostic criteria, and developing targeted therapies. Researchers are also studying the long-term effects of ATS and the factors that influence disease severity.

How is periodic paralysis managed?

Lifestyle changes, such as adjusting diet and exercise routines, may help reduce triggers associated with periodic paralysis. Management strategies are individualized based on the specific subtype, symptom patterns, and known triggers, and may include potassium supplementation or avoidance to help prevent or manage attacks.

Treatment options are limited but may include carbonic anhydrase inhibitors. Dichlorphenamide (brand name Keveyis) was approved by the FDA in 2015 for hypoPP and hyperPP. These medications have been used in periodic paralysis management for many years, although their exact mechanism is not fully understood.

MDA educational resources

• Periodic Paralysis Treatment Fact Sheet

Additional reading

• Statland JM, et al. Review of the Diagnosis and Treatment of Periodic Paralysis. Muscle Nerve. 2018 Apr;57(4):522-530. doi: 10.1002/mus.26009. Epub 2017 Nov 29. PMID: 29125635; PMCID: PMC5867231.

Last reviewed June 2026.