HMN 2026: What is the alternating hemiplegia of childhood, a rare disorder

For families of children born with alternating hemiplegia of childhood, the questions begin almost immediately: Will it get worse? How long do we have? What should we prepare for? The clearest answers yet are emerging and changing how doctors and families understand the course of a rare neurological disorder.

The research traces the natural history of alternating hemiplegia of childhood (AHC), a condition so rare that it affects roughly one in a million children worldwide. A study by Duke University School of Medicine clarifies what clinicians could only guess and reinforces why early intervention and careful monitoring may be critical. The work is published in the journal Annals of the Child Neurology Society.

“This is the kind of information families have been asking about for decades,” said senior study author Mohamad Mikati, MD, professor of pediatrics and neurobiology who has helped build one of the most robust AHC clinics in the world at Duke Health. “We finally have a clearer picture of the trajectory.”

A disorder defined by uncertainty

AHC typically appears in infancy, often before a child’s first birthday. It is marked by recurring episodes of paralysis, affecting one side of the body or the other, or both—along with seizures, abnormal movements, cognitive impairment, and development delays.

For decades, doctors could diagnose AHC only by its symptoms. In the 1990s, Mikati identified the first hereditary family with the disease, proving it was genetic and launching national AHC patient registries, including one at Duke. But families were still left without answers about why it occurred, how fast it progressed or what families should expect long term.

That began to change in 2012, when Mikati joined an international team led by former Duke geneticist David Goldstein, Ph.D., to identify mutations in the ATP1A3 gene as the cause of AHC in most patients. The gene affects a critical neural “pump” needed to meet the brain’s energy demands.

But understanding the genetic cause did not immediately answer the most pressing question: What happens over a lifetime?

To find out, researchers evaluated 115 patients ranging from infancy to 46 years old, drawing from nine medical centers across five countries. Using standardized neurological and developmental assessments, and following many patients for up to three additional years, the team asked a fundamental question: Does AHC progress, and if so, when?

AHC does worsen over time, but not steadily throughout life. Instead, the disease appears to exert its greatest and most damaging effects during a distinct window in early childhood—between ages 1 and 5.

During those years, children experienced significant declines in intellectual functioning and non-episodic disability—the everyday cognitive and physical challenges that exist outside of sudden paralysis attacks. Adaptive behaviors, including communication and daily living skills, also worsened.

After age 5, however, that decline largely stabilized. Intellectual and functional scores did not continue to deteriorate through later childhood and adulthood.

For families, that distinction matters.

“What we’re seeing is not a condition that continues to worsen indefinitely,” said lead study author Shital Patel, MD, a pediatric neurologist specializing in epilepsy at Duke Health. “It’s a disease with a critical early phase that defines much of the long-term outcomes.”

What gets better—and what doesn’t

Not every part of the disease followed the same pattern.

Underlying motor impairment, which is difficulty with movement, remained largely stable across age groups. So did dystonia, the involuntary muscle contractions that can twist the body into painful positions.

There was, however, an encouraging finding.

The severity of paralysis episodes improved after age 5. Attacks did not disappear, but they became less intense and less disabling over time.

For parents who spend early childhood bracing for sudden collapses, hospital visits and emergency medications, that nuance offers a measure of relief. While baseline challenges often persist, some of the most frightening symptoms may ease as children grow older.

Predicting the future

Duke authors Lyndsey Prange, April Boggs, Joan Jasien, Beiyu Liu, and Hwanhee Hong contributed to the natural history study that also identified key factors that influence long-term outcomes—information that could transform how clinicians counsel families.

Children who developed epilepsy fare significantly worse across multiple measures, including intellectual ability, motor function, and non-paroxysmal disability. Early severity mattered as well: children with greater impairment in early life were more likely to experience outcomes later.

Genetics also played a role. Specific ATP1A3 mutations were linked to characteristic patterns of severity. The D801N mutation was associated with more severe episodic disability, while the E815K mutation correlated with greater intellectual impairment.

Over time, those distinctions may help doctors tailor monitoring strategies, prioritize seizure control, and design personalized therapies.

Perhaps more urgently, the study addressed a question many families are afraid to ask outright: Is AHC life-threatening?

Researchers identified a mortality rate of 1.12 deaths per 100 patient years. Sudden unexpected death in epilepsy (SUDEP) occurred at a rate of 6.5 deaths per 1,000 patient years—a meaningful and concerning figure for a pediatric neurological condition.

Those findings highlight the importance of epilepsy management and long-term monitoring, not just to improve the quality of life, but to save lives.

Why this moment matters

Rare diseases often suffer from a lack of long-term data. Without knowing how a condition unfolds, doctors struggle to guide families; researchers lack endpoints for clinical trials and funding agencies underestimate urgency.

By defining when AHC progresses most sharply, identifying predictors of outcome and documenting mortality risk, this study advances the medical understanding of the disease. It also reframes AHC itself, Patel said, not as a static disorder punctuated by isolated episodes, but as a condition with progressive elements concentrated in early childhood.

That shift is already influencing research. Mikati said Duke scientists are now exploring gene-targeted therapies and early-intervention strategies designed specifically for that vulnerable window.

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