Childhood Movement Disorders: The Impact of ATP1A3 Gene Mutations — The Movement Disorder Journal and News

Movement disorders affect people of all ages, including the youngest.

Movement disorder diseases affect millions worldwide. Many, such as Huntington’s and Parkinson’s diseases, typically impact adults, presenting symptoms like dystonia, freezing gait, resting tremor, bradykinesia, impaired coordination, and rigidity. However, there is a group of rare movement disorders that begin in very young children, all linked to the ATP1A3 gene, with symptoms starting as early as 6 to 7 months old. These disorders can affect infants, children, adolescents, and adults, with these symptoms often developing gradually with age.

The discovery of ATP1A3 dates back to the 1980s and 1990s, when researchers studying how cells move sodium and potassium ions across their membranes identified a neuron-specific form of the sodium–potassium pump — one that would later prove essential to brain signaling. In 2004, scientists linked mutations in ATP1A3 to rapid-onset dystonia-parkinsonism. Several years later, in 2012, another breakthrough connected these mutations to alternating hemiplegia of childhood. In these conditions, weakness on one side of the body, known as Hemiparesis, can make movement difficult and uncoordinated. In more severe cases, this can progress to Hemiplegia, where one entire side of the body becomes paralyzed. These episodes can alternate from one side of the body to the other, often beginning in infancy and continuing throughout life.

This rare genetic disorder actually refers to a group of rare neurological conditions caused by mutations in the ATP1A3 gene, which plays a central part in how brain cells function. The ATP1A3 gene provides instructions for a system in the brain called the sodium-potassium pump. This “pump,” acting like a battery, is responsible for keeping brain cells electrically charged, allowing brain cells to reset after firing, and helping nerve cells send messages to each other, keeping the right balance of electrical activity in the brain. This is yet another system in the body that helps support smooth, controlled body movements. When there is a disruption in this system, brain signals become unstable, leading to movement problems that may be persistent over time or come and go.

ATP1A3 isn’t just one disease; it is a spectrum of related neurological conditions caused by mutations in the same gene, and changes in the same gene can lead to very different symptoms from person to person. These can include Alternating hemiplegia of childhood (AHC) (symptoms starting before 18 months), Rapid-onset dystonia-parkinsonism (RDP) (as early as 9 months), CAPOS syndrome (starting from 6 months to age 5 and is often triggered by fever), and RECA / FIPWE (Relapsing Encephalopathy with Cerebellar Ataxia), and FIPWE (Fever-Induced Paroxysmal Weakness and Encephalopathy, which can start from infancy to age 5, with some cases seen later in the teenage years or adulthood. In addition to these known forms, researchers have found that symptoms can overlap and continue to expand, with some children displaying more severe symptoms early in life and others having ongoing problems between episodes. This supports the idea that ATP1A3 is not made up of separate conditions, but instead exists on a spectrum where symptoms can vary widely from person to person.

ATP1A3-related conditions often show up as a mix of sudden episodes and longer-lasting neurological problems, meaning the condition doesn’t look the same all the time. Sudden episodes are short and often unpredictable events in which a child can experience sudden abnormal movements that can last for minutes, hours, or even days, and then improve, with longer-lasting symptoms that don’t fully go away once the abnormal movements subside. Examples of these include attacks of weakness, paralysis, or abnormal movements that are accompanied by seizures, abnormal eye movements, or difficulty with coordination. Children and adults living with ATP1A3-related disorders can develop longer, more persistent challenges, including motor impairment, speech and swallowing difficulties, and experience challenges in learning, thinking, social skills, recognizing people, forming sentences, solving simple problems, and basic physical skills like rolling over, sitting, or walking.

Sodium–potassium pump By Andrei Lomize — Own work. Protein image from OPM database, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=34170807

Rapid-onset dystonia-parkinsonism is another recognized form of the ATP1A3-related disease, demonstrating how mutations in this gene can mimic more familiar conditions like Parkinson’s disease that often appear suddenly or over a short period of time. These symptoms generally develop during a person’s teenage years or early adulthood, but other ages are not excluded. These symptoms include Dystonia, problems with speech or swallowing, and Parkinson type symptoms such as slowed movement and trouble with balance. In many cases, the onset can be triggered by physical stress, illness, or emotional stress, with symptoms progressing over hours to days rather than years. Unlike Parkinson’s disease, these symptoms typically stabilize after the initial onset instead of continuing to gradually worsen, and they often respond poorly to standard Parkinson’s treatments.

Diagnosis of this rare movement disorder involves a neurological exam that is performed to assess patient movement, muscle tone, coordination, reflexes, and speech. These exams help rule out other neurological conditions that may look similar because symptoms of ATP1A3 can mimic other conditions like epilepsy, cerebral palsy, or even Parkinson-like disorders. Because of this, genetic testing is the best way to determine whether a mutation in the ATP1A3 gene is present and to confirm an accurate diagnosis by use of advanced sequencing techniques like next-generation sequencing or whole exome sequencing. In many cases, imaging tests like MRI scans and EEG studies can also be used to support the evaluation and to help rule out other causes, even though they may appear normal in ATP1A3-related conditions.

While there is no cure in a traditional sense, management of symptoms involves stabilizing brain signaling rather than curing the underlying genetic mutation. By controlling movement symptoms like those associated with Dystonia and Parkinsonism, and preventing triggers such as stress, fatigue, and fever. Medications, including flunarizine, benzodiazepines, and muscle relaxants, may help ease symptoms, but the responses to treatment vary widely from patient to patient, and in some cases, anti-seizure medications may also be used depending on the symptoms. Sleep helps play a critical role for those with the disorder by helping the brain reset itself, and in some cases, may temporarily reduce or stop episodes. Long-term care often includes physical, occupational, and speech therapy, requiring a team-based approach from multiple specialists to help manage symptoms, with care often tailored to each individual based on how the disease presents and progresses over time.

ATP1A3 Mutation/Media by Chris Denny-ChatGPT

Originally published at https://themovementdisorderjournal.com on March 20, 2026.