Alternating hemiplegia of childhood is a rare neurological disorder that causes temporary paralysis episodes, often affecting different sides of the body, along with developmental challenges and other symptoms that require lifelong medical attention.

Understanding the Frequency of This Rare Condition

Alternating hemiplegia of childhood, often shortened to AHC, is an extremely uncommon neurological disorder. The condition affects approximately one in every one million people, making it one of the rarer medical conditions that healthcare professionals encounter.^[1] Some research suggests the prevalence may be somewhat higher, possibly affecting one in every 100,000 children up to the age of 16, though this estimate is likely still lower than the actual number of cases due to underdiagnosis.^[7]

Originally, experts believed the condition occurred in about one in a million individuals. However, recent research has suggested there may be as many as 28,000 cases of AHC worldwide. Despite this potentially higher number, only around 1,500 cases have been properly identified and documented, which means thousands of people may be living with undiagnosed AHC.^[15] This significant gap between estimated and confirmed cases highlights a major challenge in diagnosing this rare condition.

The rarity of alternating hemiplegia of childhood means that many healthcare providers may have limited or no experience with the condition. This unfamiliarity can lead to delays in diagnosis or even misdiagnosis. Many patients are initially thought to have epilepsy because some symptoms of AHC, particularly the muscle stiffness during episodes, can resemble epileptic seizures. Similarly, the weakness that occurs during AHC episodes can look like the weakness that sometimes follows seizures.^[2]

Awareness of alternating hemiplegia of childhood has been increasing in recent years among the medical community. This growing recognition has led to more frequent early diagnoses compared to the past. Getting an accurate diagnosis as soon as possible is essential because it helps families avoid unnecessary medications that may have negative side effects, and it allows children to receive appropriate treatments and support services more quickly.^[2]

What Causes Alternating Hemiplegia of Childhood

Alternating hemiplegia of childhood is primarily a genetic condition. The vast majority of cases, approximately 75 to 80 percent, are caused by mutations in a gene called ATP1A3.^[1][6] This gene provides instructions for making a specific protein that plays a critical role in how brain cells function. The protein forms part of a larger complex called Na+/K+ ATPase, which acts like a pump that moves sodium and potassium ions in and out of nerve cells.

The movement of these charged particles is essential for the normal functioning of neurons, which are the cells in the brain that send signals to control muscle movement and other bodily functions. When the ATP1A3 gene has a mutation, the Na+/K+ ATPase pump doesn’t work properly. This malfunction impairs the ability of brain cells to transport ions normally, though scientists are still working to understand exactly how this leads to the paralysis episodes and other symptoms characteristic of AHC.^[1]

The ATP1A3 gene is highly expressed in specific regions of the brain that influence the autonomic nervous system, which controls automatic body functions like heart rate, breathing, and digestion.^[6] This may help explain why people with AHC experience not only paralysis but also other symptoms affecting various body systems.

In rare instances, alternating hemiplegia of childhood can be caused by mutations in a different but similar gene called ATP1A2.^[1] Some patients have also been identified with mutations in other genes including RHOBTB2, CLDN5, SCN2A, SLC2A1, and TBC1D24, though these are even less common.^[7] In approximately 20 to 25 percent of patients, the exact genetic cause remains unknown despite testing.^[6]

Most cases of alternating hemiplegia of childhood result from new mutations that occur spontaneously. This means the genetic change happens at or shortly after conception and is not inherited from either parent. These are called de novo mutations. People with AHC typically have no family history of the disorder.^[1][15] The ATP1A3 gene mutation is usually spontaneous, meaning it rarely runs in families.^[3]

However, the condition can occasionally run in families. When this happens, the pattern of inheritance is considered autosomal dominant, which means having just one copy of the altered gene in each cell is sufficient to cause the disorder. Interestingly, when alternating hemiplegia of childhood affects multiple family members, the signs and symptoms are typically milder than when a single individual is affected for unknown reasons.^[1]

The specific mutation within the ATP1A3 gene can affect the severity of symptoms. The three most common mutations are D801N, E815K, and G947R at the protein level. Research has shown that these different mutations reflect varying degrees of symptom severity, with E815K being associated with more severe neurological symptoms, D801N with moderate severity, and G947R with milder presentations.^[6]

Risk Factors for Developing AHC

Because alternating hemiplegia of childhood is primarily caused by spontaneous genetic mutations that occur randomly, there are no clearly identified risk factors that increase the likelihood of a child developing this condition. The mutations in the ATP1A3 gene or other associated genes happen by chance during conception or early development, rather than being influenced by environmental exposures, parental behaviors, or lifestyle factors.

The condition does not appear to affect one gender more than the other, nor does it show preferences for particular ethnic or racial groups. Since most cases result from new mutations rather than inherited genetic changes, having a family history of AHC is uncommon. Parents of a child with alternating hemiplegia of childhood typically have normal genes and did not pass on a mutated gene to their child.

In the rare instances where AHC does run in families, having a parent with the condition or a mutation in the ATP1A3 gene would represent a risk factor. In these cases, there would be a 50 percent chance that the affected parent could pass the genetic mutation to each child, given the autosomal dominant inheritance pattern. However, these familial cases are the exception rather than the rule.

Recognizing the Symptoms

The symptoms of alternating hemiplegia of childhood typically begin very early in life. Most children with AHC develop symptoms before they reach 18 months of age, though the initial signs may appear in early infancy.^[1] The condition is characterized by recurring episodes of temporary paralysis, which is where the disorder gets its name. During these episodes, the paralysis often affects one side of the body, a condition called hemiplegia. Sometimes the paralysis switches from one side to the other, or it can affect both sides of the body at the same time.^[1]

These paralysis episodes can vary significantly in how long they last. Some episodes may be brief, lasting only minutes, while others can persist for days.^[1] The frequency of episodes also varies greatly from person to person, with some individuals experiencing attacks daily and others having them less often. Episodes can range from causing mild weakness to complete paralysis on one or both sides of the body.^[4]

One of the most distinctive features of alternating hemiplegia of childhood is that symptoms typically disappear completely when the affected person falls asleep. However, the symptoms often return shortly after the person wakes up, particularly if the episode was severe.^[1][2] This pattern of symptoms resolving with sleep but potentially recurring upon awakening is a hallmark characteristic that helps doctors distinguish AHC from other conditions.

In addition to paralysis, children with AHC experience sudden attacks of uncontrollable muscle activity. These can cause involuntary limb movements, a condition called choreoathetosis, which involves jerky or worm-like movements of the arms and legs. Muscle tensing, known as dystonia, causes episodes of painful muscle stiffness. Many children also experience abnormal eye movements called nystagmus, and some may have episodes of shortness of breath, or dyspnea.^[1] These attacks can occur during paralysis episodes or separately.

Most patients with alternating hemiplegia of childhood experience episodes of abnormal, jerky eye movements and trouble with balance or walking. Gastrointestinal issues, particularly constipation, are also common.^[2] Some children experience sudden changes in skin color and temperature, including sudden redness and warmth called flushing, unusual paleness called pallor, sweating, and changes in skin color.^[1]

About half of children with AHC eventually develop true epileptic seizures in addition to their other symptoms. They may also have episodes where they seem less aware of their surroundings, behavioral issues such as aggression, and sleep disorders.^[2] Seizures can be triggered by psychological stress, excitement, or exposure to water, heat, or cold temperatures.^[2]

Fewer than half of patients experience swallowing disorders, autism spectrum disorder, or the involuntary jerky or worm-like movements of the arms and legs mentioned earlier.^[2] Paralysis is often accompanied by problems with speaking, eating, and swallowing, which can lead to patients with AHC being frequently underweight due to these eating difficulties.^[4]

All children with alternating hemiplegia of childhood experience some degree of developmental delay and intellectual disability. These cognitive problems can range from mild to severe. Almost all affected individuals have delays affecting learning, movement, and behavior, and their cognitive functioning typically declines over time.^[1][2] Many children with AHC show symptoms similar to attention deficit hyperactivity disorder (ADHD).^[2]

The number and length of episodes typically worsen throughout early childhood but may begin to decrease over time. Some of the uncontrollable muscle movements may disappear entirely as children grow older, though the episodes of paralysis generally continue throughout life.^[1] Patients may lose developmental milestones during prolonged attacks, but most gradually regain them slowly over weeks or months.^[7]

Various factors can trigger episodes of paralysis or uncontrolled movements. Common triggers include stress, extreme tiredness, cold temperatures, bathing, illness, excitement, noise, and bright lights, though sometimes the trigger is not apparent.^[1][7]

Preventing Alternating Hemiplegia of Childhood

Currently, there is no known way to prevent alternating hemiplegia of childhood. Because the condition is caused by spontaneous genetic mutations that occur randomly, there are no preventive measures that expectant parents can take to reduce the risk of their child developing AHC. The genetic changes that lead to this disorder happen by chance during conception or very early development and are not influenced by anything the parents did or could have avoided.

Since most cases result from new mutations rather than inherited ones, genetic screening or testing of parents before pregnancy would not be helpful in predicting whether a child will develop the condition. Even in families where one child has been diagnosed with alternating hemiplegia of childhood, the likelihood of having another child with the same condition is extremely low because the mutation typically occurs spontaneously rather than being passed down.

However, in the rare families where AHC appears to be inherited in an autosomal dominant pattern, genetic counseling may be valuable. Families with a known history of the condition might benefit from discussing their situation with a genetic counselor who can explain the risks and available options. Advanced genetic analysis and counseling services are available at some specialized medical centers.^[3]

While the condition itself cannot be prevented, early diagnosis and intervention can make a significant difference in managing symptoms and supporting development. Parents who notice unusual symptoms in their infant or young child, particularly recurring episodes of weakness, paralysis, or abnormal movements, should seek medical evaluation promptly. Early diagnosis allows families to access appropriate treatments, therapies, and support services that can improve quality of life, even though they cannot prevent or cure the underlying condition.

How the Body’s Normal Functions Are Affected

To understand alternating hemiplegia of childhood, it helps to know how nerve cells normally work. Neurons, which are the cells in the brain and nervous system, communicate with each other through electrical and chemical signals. These signals control everything from muscle movement to automatic functions like breathing and heart rate. For neurons to send these signals properly, they need to carefully control the balance of charged particles called ions, particularly sodium and potassium, inside and outside the cell.

The Na+/K+ ATPase pump is a critical protein complex that maintains this balance. It works like a revolving door, pushing sodium ions out of the neuron while bringing potassium ions in. This constant pumping activity creates an electrical difference across the cell membrane, which is essential for the neuron to send signals. When a neuron needs to transmit a message, it briefly allows sodium to rush back in, creating an electrical signal that travels along the nerve cell. After the signal passes, the Na+/K+ ATPase pump works to restore the original balance, preparing the neuron to send the next signal.^[1]

In people with alternating hemiplegia of childhood, mutations in the ATP1A3 gene mean that the Na+/K+ ATPase pump doesn’t work as efficiently as it should. When this pump malfunctions, neurons cannot properly regulate the movement of sodium and potassium ions across their membranes. Brain cells become unable to move these ions normally, as they should.^[2] This disruption affects the neuron’s ability to maintain its normal electrical state and to send signals correctly.

The reduced activity of the Na+/K+ ATPase can lead to several downstream effects on brain function. The impaired ion transport may increase intracellular calcium levels through interactions with voltage-gated calcium channels and sodium-calcium exchangers. These changes affect how neurons communicate with each other and can increase neuron excitability, potentially leading to abnormal patterns of brain activity.^[6] Some of the channels involved in this disorder include N-type voltage-gated calcium channels, ATP-sensitive potassium channels, and the sodium-calcium exchanger.^[6]

Because the ATP1A3 protein is primarily expressed in certain types of brain cells called GABAergic inhibitory interneurons, its reduced function particularly affects the brain’s ability to regulate and inhibit excessive neuronal activity. When these inhibitory neurons don’t work properly, it can increase overall brain excitability. This may result in spreading depolarization, a wave of electrical activity that moves through the brain tissue, potentially causing the paralysis episodes and other symptoms seen in AHC.^[7]

The ATP1A3 gene is highly expressed in brain regions that influence the autonomic nervous system, including the cortex, basal ganglia, and cerebellum, and to some extent in the heart.^[6] This distribution pattern helps explain why alternating hemiplegia of childhood affects not just movement but also autonomic functions like heart rate, breathing patterns, skin color changes, and temperature regulation.

Scientists are still working to understand exactly how the malfunctioning Na+/K+ ATPase leads to the specific pattern of symptoms seen in AHC. The relationship between the genetic mutation and the clinical features remains an active area of research. What is clear is that the disrupted ion balance in neurons affects their ability to function normally, control muscle movement, regulate automatic body functions, and support normal brain development. This widespread disruption of normal neuronal function explains the broad range of symptoms experienced by people with alternating hemiplegia of childhood, from paralysis episodes to developmental delays to problems with various body systems.

Alternating hemiplegia of childhood is not considered to be progressive in nature, nor is it typically life-shortening. However, some individuals have lost their lives prematurely from complications related to the disease, including loss of ability to breathe, seizures, heart issues, or injuries from loss of motor control.^[15] The condition requires lifelong care, and while problems may increase over time, various treatments and therapies can make a significant difference in patients’ lives.^[2]