Alternating hemiplegia of childhood (AHC)
A rare, severe paroxysmal disorder of childhood — episodes of alternating hemiplegia, dystonia, oculomotor abnormalities and epilepsy, most often caused by ATP1A3 mutations.
Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder that begins before 18 months of age, characterised by recurrent transient episodes of hemiplegia affecting either side of the body (and sometimes both), dystonic attacks, abnormal eye movements, autonomic features and epilepsy. Around three-quarters of cases are caused by de novo heterozygous mutations in ATP1A3, encoding the catalytic α3 subunit of the neuronal Na⁺/K⁺-ATPase. Trigger avoidance, flunarizine and seizure control are mainstays of current care.
At a glance
- Onset
- Before 18 months of age
- Gene
- ATP1A3 (de novo, autosomal dominant) in ~75% — also DNM1L, RHOBTB2 and others
- Cardinal features
- Alternating hemiplegia, dystonia, oculomotor abnormalities, paroxysmal episodes triggered by stress, sleep relieves attacks
- Epilepsy
- In around 50% of children; often refractory
- Prevalence
- ~1 in 1,000,000
What AHC is
Alternating hemiplegia of childhood is defined by a distinctive cluster of paroxysmal episodes starting before 18 months: hemiplegic attacks that affect either side of the body and can shift mid-attack, attacks of bilateral plegia, dystonic attacks (often painful), abnormal eye movements (nystagmus, strabismus, ocular motor apraxia), autonomic disturbances (skin colour changes, breathing irregularity, temperature dysregulation) and developmental impairment. A central diagnostic clue is that the episodes characteristically resolve with sleep and then sometimes recur on waking.
Around 75% of cases are caused by de novo heterozygous mutations in ATP1A3. Other genes (DNM1L, RHOBTB2, ATP1A2, CACNA1A, SLC1A3) account for a minority of clinically similar presentations. The ATP1A3 spectrum also includes rapid-onset dystonia-parkinsonism and CAPOS syndrome.
How the diagnosis is made
Diagnosis is clinical, supported by the Aicardi criteria and confirmed genetically. ATP1A3 is included in modern movement-disorder and epilepsy gene panels and is reliably picked up by whole-exome and whole-genome sequencing. Brain MRI is typically normal in classical AHC; serial EEG may capture the ictal pattern of an episode and identify any associated epilepsy.
Differential diagnosis includes mitochondrial disease, glucose transporter type 1 (GLUT1) deficiency, hemiplegic migraine, focal status epilepticus, and paroxysmal dyskinesias. Many of these are treatable, so the work-up needs to be thorough.
Trigger management and acute attack care
Trigger avoidance is the cornerstone of practical care. Common triggers include bathing, temperature change, certain foods, fluorescent lighting, emotional stress, infection and physical activity. Families are taught to recognise and minimise individual triggers. Acute attacks are managed by removing the trigger, providing a calm dark quiet environment, and — where appropriate — encouraging sleep, which characteristically aborts attacks.
Treatment today
Flunarizine, a calcium-channel blocker, is the most commonly used medication and reduces episode frequency and severity in a substantial proportion of children, though access varies by country. Other agents (topiramate, acetazolamide, memantine, aripiprazole and others) have been used as add-on therapy in selected children. For the epilepsy phenotype, antiseizure medications are chosen for the seizure type; sodium-channel blockers can be useful in some children and provoke episodes in others, so adjustments require close monitoring.
Multidisciplinary care — physiotherapy, occupational therapy, communication support, swallowing assessment, behaviour and education — is part of the long-term plan.
AHC episodes are not seizures in most cases. Differentiating them from focal epileptic events is part of why a paediatric-neurology-led evaluation matters.
Precision-medicine pipeline
Research into ATP1A3-targeted therapies is active: gene therapy approaches, antisense oligonucleotide strategies, and small molecules acting on Na⁺/K⁺-ATPase function are at preclinical or early clinical stages. Patient organisations (AHC Foundation, AHCF, Patient Voice) maintain registries and follow the pipeline closely.
How an educational review can help
AHC is so rare that even experienced clinicians may have seen only a handful of children. An educational review can pull together the current literature, frame the medication options and trigger-management strategy, summarise the precision-medicine pipeline honestly, and prepare focused questions for your treating team.
It is educational — not a diagnosis, treatment or prescription — and does not replace the care of your child's own clinicians.
Selected sources
- Heinzen EL et al. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet. 2012;44:1030–1034.
- Panagiotakaki E et al. Evidence of a non-progressive course of AHC: data from a multicentre cohort. Brain. 2010 + updates.
- Sweney MT et al. Alternating hemiplegia of childhood: early characteristics, course, and treatment response. Pediatrics. 2009.
- Capuano A et al. Alternating hemiplegia of childhood: understanding the genotype-phenotype relationship of ATP1A3 variations. Appl Clin Genet. 2015.
- Heimer G et al. The ATP1A3 disease spectrum: review and consensus 2023.
Last reviewed: 2026-05-28
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