Ataxia-oculomotor apraxia type 4

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ORPHA:459033OMIM:616267G60.2
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Overview

Ataxia-oculomotor apraxia type 4 (AOA4) is a very rare inherited neurological condition that affects the brain and nervous system. It belongs to a group of disorders called ataxia-oculomotor apraxias, which share two main features: progressive difficulty with coordination and balance (ataxia) and trouble moving the eyes voluntarily to look at things (oculomotor apraxia). AOA4 is caused by mutations in the PNKP gene, which plays an important role in repairing damaged DNA in our cells. When this gene does not work properly, nerve cells in the brain — especially in the cerebellum, the part that controls balance and coordination — gradually break down over time. People with AOA4 typically begin showing symptoms in childhood or adolescence. Early signs often include unsteady walking, frequent stumbling, and difficulty with eye movements. Over time, the condition tends to worsen, and individuals may develop additional neurological problems such as peripheral neuropathy (damage to nerves in the hands and feet causing numbness or weakness), dystonia (involuntary muscle contractions), and sometimes cognitive difficulties. Some patients may also have elevated levels of certain proteins in their blood, such as alpha-fetoprotein or albumin, which can help with diagnosis. Currently, there is no cure for AOA4. Treatment focuses on managing symptoms and maintaining quality of life. Physical therapy, occupational therapy, and speech therapy can help patients maintain function for as long as possible. Research into DNA repair disorders is ongoing, and understanding of this condition continues to grow.

Also known as:

Key symptoms:

Progressive difficulty with balance and coordination (ataxia)Trouble moving the eyes voluntarily (oculomotor apraxia)Unsteady or wobbly walkingNumbness or tingling in hands and feet (peripheral neuropathy)Muscle weakness in the limbsInvoluntary muscle contractions or abnormal postures (dystonia)Slurred or slow speechDifficulty with fine motor tasks like writing or buttoning clothesReduced reflexesPossible mild cognitive difficultiesElevated blood levels of alpha-fetoproteinCerebellar atrophy visible on brain MRI

Clinical phenotype terms (21)— hover any for plain English
DyscalculiaHP:0002442DyslexiaHP:0010522TelangiectasiaHP:0001009Abnormal saccadic eye movementsHP:0000570Abnormal toe morphologyHP:0001780
Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Childhood

Begins in childhood, roughly ages 1 to 12

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Ataxia-oculomotor apraxia type 4.

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No actively recruiting trials found for Ataxia-oculomotor apraxia type 4 at this time.

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No specialists are currently listed for Ataxia-oculomotor apraxia type 4.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Ataxia-oculomotor apraxia type 4.

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Community

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Caregiver Resources

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Social Security Disability

Learn how rare disease patients may qualify for SSDI/SSI benefits.

Questions for your doctor

Bring these to your next appointment

  • Q1.How quickly is this condition likely to progress in my child's case?,What therapies should we start right away to maintain function?,Are there any clinical trials or research studies we could participate in?,What signs should we watch for that would indicate the disease is getting worse?,Should other family members be tested for carrier status?,What school or workplace accommodations would you recommend?,How often should we schedule follow-up visits and brain imaging?

Common questions about Ataxia-oculomotor apraxia type 4

What is Ataxia-oculomotor apraxia type 4?

Ataxia-oculomotor apraxia type 4 (AOA4) is a very rare inherited neurological condition that affects the brain and nervous system. It belongs to a group of disorders called ataxia-oculomotor apraxias, which share two main features: progressive difficulty with coordination and balance (ataxia) and trouble moving the eyes voluntarily to look at things (oculomotor apraxia). AOA4 is caused by mutations in the PNKP gene, which plays an important role in repairing damaged DNA in our cells. When this gene does not work properly, nerve cells in the brain — especially in the cerebellum, the part that c

How is Ataxia-oculomotor apraxia type 4 inherited?

Ataxia-oculomotor apraxia type 4 follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Ataxia-oculomotor apraxia type 4 typically begin?

Typical onset of Ataxia-oculomotor apraxia type 4 is childhood. Age of onset can vary across affected individuals.