SCA1 Fact Sheet
Ataxia:
SCA1 (Spinocerebellar Ataxia Type 1)
RELATED GENES:
ATXN1
MUTATION TYPE:
ATXN1 -> CAG expansion mutation
LOCATION:
Chromosome 6 (6p22.3)
INHERITANCE:
Autosomal Dominant
LAST UPDATE:
March 16, 2025 by Marcio Galvão
Content generated with the support of Generative AI, reviewed by the author.
1. ABOUT SCA1
Spinocerebellar Ataxia Type 1 (SCA1) is a rare, serious, neurodegenerative, and hereditary disorder of the central nervous system. The pathogenesis of SCA1 is associated with mutations in the ATXN1 gene, located on chromosome 6 (6p22.3), which lead to alterations in the synthesis of the ataxin-1 protein. Ataxin-1 plays a crucial role in transcriptional regulation and RNA processing, particularly in cerebellar neurons. It operates within the cell nucleus, interacting with other proteins and complexes involved in gene expression.
When a mutation occurs in the ATXN1 gene (specifically, an abnormal expansion of CAG repeats), the resulting ataxin-1 protein becomes structurally altered, containing an elongated chain of glutamines (polyQ). These misfolded proteins tend to accumulate in the nucleus of nerve cells, forming toxic aggregates that lead to cellular dysfunction and neuronal death.
Among the most affected are the Purkinje cells in the posterior vermis of the cerebellum, which are particularly vulnerable compared to other cerebellar regions. These cells are essential for motor control. Over time, cumulative neuronal loss results in cerebellar atrophy and the typical symptoms of ataxia, such as loss of motor coordination [1].
Image credit: Diagram generated by the author with support from Artificial Intelligence.
2. TYPICAL SYMPTOMS
The symptoms experienced in SCA1 and their severity can vary from person to person, even within the same family. The following list is for reference only.
Initial symptoms
The first symptoms of SCA1 are typically a lack of manual coordination and problems with balance when walking, as cerebellar ataxia affects both gross motor coordination (gait) and fine motor coordination (writing, object manipulation). Studies highlight dysmetria (error in reaching for objects) and dysdiadochokinesia (difficulty with rapid alternating movements) as early signs. Difficulty with writing (fine motor skills) is caused by the degeneration of Purkinje cells, which compromise fine motor control.
Disease progression
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As SCA1 progresses over several years, degeneration of the cerebellar nuclei and brainstem may occur, leading to slurred speech (ataxic dysarthria) and difficulty swallowing (dysphagia).
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In some cases, peripheral neuropathy (loss of sensation and reflexes in the feet or legs) may be a possible late manifestation. Reduced reflexes and vibration sensitivity may occur, especially in advanced stages.
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Spasticity and muscle stiffness may also occur, although these are less typical symptoms in SCA1, which is predominantly hypotonic (reduced muscle tone). Spasticity is more common in other SCAs (such as SCA3).
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Eye disorders (especially nystagmus. Diplopia is less relevant in SCA1 compared to SCA3).
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Mild to moderate cognitive impairments (with deficits in executive functions and memory) may manifest but are not predominant in SCA1.
Pathology and clinical aspects
For a more technical list of the symptoms and usual clinical aspects of SCA1, consult references [2, 3, 9] .
3. ONSET
The onset of symptoms of SCA1 usually occurs in early adulthood, between 30 and 40 years of age, on average. However, cases of pediatric manifestation (in childhood/adolescence) or in older adults (over 50 years of age) have also been described. Thus, SCA1 can manifest in different age groups, although the classic presentation is in adulthood [2]. The Neuromuscular portal [3] indicates the range between 4 and 74 years of age, with an average around the fourth decade of life.
In pediatric cases, associated with very long CAG expansions (>70 repeats), symptoms are more severe and progress rapidly. See 4. Anticipation .
4. ANTICIPATION
The unstable expansion of CAG repeats in the ATXN1 gene may lead to earlier onset in offspring, especially in paternal transmission (due to greater meiotic instability in sperm). In SCA1 ataxia, the onset of symptoms may be up to 10 years earlier than in one generation [10] .
Pediatric cases of SCA1 can occur but are rare, and are associated with very long CAG expansions (>70 repeats) and present with severe symptoms such as epilepsy and accelerated motor regression (Rivaud-Péchoux, S. et al. (1998). Severe infantile phenotype of spinocerebellar ataxia type 1 . Neurology). See Note below.
Note: Generally speaking, if the number of CAG repeats in the genetic mutation is higher, symptoms tend to appear earlier (Please see Section 5. Inheritance ) and perhaps with greater severity. However, this is an "average" figure, not an absolute truth for all patients individually . Factors other than the number of CAG repeats can influence the age at which symptoms appear, their severity, and the rate of disease progression, such as genetic factors (perhaps the person has other genetic characteristics that protect them from certain problems) and environmental factors (quality of life, stress level, diet, etc.).
5. INHERITANCE
SCA1 is an autosomal dominant disorder. This means that individuals of any sex have an equal chance of inheriting one copy (allele) of the mutated gene and becoming carriers of the mutation. A child of a person with SCA1 has a 50% chance of inheriting a copy of the altered gene (assuming that only one parent—either the biological mother or father—carries the mutation).
It’s important to note that a person may inherit a gene variant and not develop the disease (i.e., remain asymptomatic), particularly if the mutation is small and falls within an intermediate range with low penetrance. However, when the inherited mutation falls within a pathogenic range (high penetrance), the disease will manifest at some point in life.
CAG Repeat Ranges in SCA1
Each individual has two copies of the ATXN1 gene, one inherited from each parent. For example:
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One allele might have 14 CAG repeats interrupted by CAT codons — this is normal and not disease-causing.
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Another allele might have 72 uninterrupted CAG repeats, which is pathogenic and causes SCA1.
Genetic Criteria for SCA1:
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Normal (non-pathogenic): 6–44 CAG repeats with CAT interruptions
(CAG repeats may be interrupted by 1–3 CAT codons, which help stabilize the sequence and prevent meiotic expansion) -
Risk range (intermediate): 35–44 uninterrupted CAG repeats
(These alleles are at risk of expanding into the pathogenic range during hereditary transmission, especially through paternal inheritance) -
Pathogenic: ≥ 45 pure CAG repeats (i.e., without CAT interruptions)
→ Results in full penetrance: individuals with ≥45 repeats will eventually develop the disease
Note: The exact CAG repeat ranges used for diagnosing SCA1 may vary between studies. For example, sources [3] and [5] report slightly different thresholds. It's also important to understand that CAG repeat length alone doesn't determine pathogenicity — the presence of CAT interruptions (which code for the amino acid leucine) in the ATXN1 gene makes a crucial difference. More precisely, CAT interruptions within the CAG repeat region act as “anchors” that stabilize the sequence and prevent its expansion during meiosis. This explains why some alleles with relatively long repeats (up to 44 CAGs) may not be pathogenic if they contain these stabilizing CAT codons.
Note: "Autosomal" means the gene is located on any chromosome other than the sex chromosomes (X and Y). Humans typically have pairs of genes — one copy inherited from the mother, the other from the father. "Dominant" means that only one copy of the mutated gene (allele) inherited from either parent is enough to transmit a trait or condition — such as a physical characteristic (e.g., dimples) or a genetic disorder (like hereditary ataxias) — to the next generation.
Image source: MedlinePlus, U.S. National Library of Medicine
6. PREVALENCE
Epidemiological studies suggest that SCA1 has a prevalence of 1 to 2 cases per 100,000 population, although these numbers can vary depending on the population studied, ethnicity, geographic location, and study methodologies. For example, applying this prevalence to the United States population (approximately 330 million people), we would have somewhere around 3,300 to 6,600 cases.
The following information on the prevalence of SCA1 is also available [3]:
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About 10% of SCAs in the world
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Highest frequency in South Africa (41%)
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Also common in Japan, India, Italy and Australia
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Not very common in Portugal, Brazil and Central Japan
It is important to note that these variations in SCA1 prevalence may be related to factors such as founder effects, historical migrations, and population-specific genetic characteristics.
7. ADDITIONAL INFORMATION
SCA1 is one of the “polyglutamine diseases” (PolyQ). It occurs when the ATXN1 gene allele inherited from one of the parents carries a mutation with an abnormally high number of CAG trinucleotide repeats (cytosine, adenine, guanine), which code for the amino acid glutamine (Q) in the protein produced by this gene. As a result, the mutant protein has an abnormal structure with an excessive glutamine tract. These malformed proteins tend to accumulate and form aggregates, particularly in the nuclei of nerve cells (neurons).
Nature has built-in defense mechanisms to "clean up" unwanted or defective proteins in cells. However, for reasons still not fully understood, these mechanisms are ineffective at clearing polyglutamine aggregates, which are insoluble through natural processes. As a result, these misfolded proteins become toxic and disrupt essential cellular functions such as:
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Autophagy
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DNA transcription
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Axonal transport
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Protein homeostasis
This ultimately leads to degeneration and death of cerebellar neurons (and other nervous system cells). The loss of neurons over time gives rise to the clinical symptoms of ataxia.
Additional Notes on PolyQ Disorders (Adapted from "Pathogenesis of SCA3 and implications for other polyglutamine diseases", Hayley S. McLoughlin et al., 2020)
1. There are currently nine known PolyQ disorders, including:
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Huntington’s Disease (HD)
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Dentatorubral-pallidoluysian atrophy (DRPLA)
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Spinal and bulbar muscular atrophy (SBMA)
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Six different spinocerebellar ataxias (SCAs): SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17
All of these diseases are caused by expanded CAG repeats in the coding regions of their respective genes and share other common features:
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Autosomal dominant inheritance (except SBMA, which is X-linked)
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Primarily affect the central nervous system (CNS), though peripheral nerves and muscles may also be involved
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Progressive course over several years
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In all PolyQ diseases, there is an inverse correlation between CAG repeat length and the age of symptom onset and disease severity — longer expansions cause earlier and more severe disease. This is linked to the phenomenon of anticipation.
2. In PolyQ diseases, misfolded proteins with expanded glutamine tracts tend to aggregate, mainly in the nuclei of neurons, although cytoplasmic and distal axonal aggregates have also been observed. The exact role of these nuclear aggregates remains unclear. One hypothesis is that they may be initially neuroprotective, but over time they become toxic (pathogenic), causing:
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Sequestration of essential proteins (e.g., transcription factors)
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Damage to mitochondria
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Disruption of the chaperone system (which helps proteins fold correctly)
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Impairment of the ubiquitin-proteasome system (UPS) (which regulates the breakdown of unwanted or damaged proteins)
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Inhibition of autophagy, a key part of cellular “quality control”
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Interference with DNA repair in the nucleus
Together, these dysfunctions impair normal neuronal function and may lead to neuronal death.
3. In addition to neurons, other cell types — such as glial cells (astrocytes, microglia, and oligodendrocytes) — may play an important role in the pathogenesis of spinocerebellar ataxias and other PolyQ diseases.
For example:
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Bergmann glia have been shown to play a key role in the degeneration seen in SCA7
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Glial alterations have also been observed in animal models of SCA1 and Huntington’s Disease, suggesting a potentially common feature among PolyQ disorders
Diagnosis - SCA1 can be diagnosed through molecular genetic testing (DNA testing) to detect abnormal CAG expansions and CAA interruptions in the ATXN1 gene. Testing is especially recommended if there is a known family history of SCA1. Before ordering genetic tests, neurologists typically perform neurological exams, evaluating symptoms, reflexes, eye movement abnormalities, and family history. Imaging studies are also commonly requested to look for cerebellar and pontine atrophy, for example.
Note: Although genetic testing can be challenging, time-consuming, and costly, it is extremely important because it allows for:
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Genetic counseling for family members (regarding inheritance risk for future generations)
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Accurate disease management, based on a definitive diagnosis
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Eligibility for clinical trials focused on developing treatments for specific types of ataxias.
8. THERAPIES AND DRUGS BEING TRIALED FOR THIS ATAXIA
View NAF Treatment Pipeline for SCA1
See also the NAF webinar " Research and Treatment Development for SCA1 ", Dr. James Orengo [8]
Learn More - Snapshot: What is an antisense oligonucleotide (ASO/AON)? NAF SCASource.
9. TREATMENTS
SCA1 ataxia currently has no cure, but its symptoms can be managed to improve quality of life and provide ongoing support to the patient. It is important that individuals with SCA1 are followed by a neurologist and a specialized multidisciplinary medical team, with the gradual inclusion of other healthcare professionals as needed, depending on symptom progression (e.g., geneticist, neuro-ophthalmologist, neurofunctional physical therapist, occupational therapist, speech therapist, nutritionist, etc.).
General Recommendations for Symptom Management in SCA1
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Many ataxia symptoms can be treated with appropriate medications, but all medications have side effects and must be prescribed by a physician.
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Neurofunctional physical therapy is highly recommended, as are exercise routines (especially stationary cycling) and regular physical activities such as yoga, Pilates, or aquatic therapy, adapted to each individual’s capacity.
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To reduce the risk of falls due to balance difficulties, the use of canes, walkers, or wheelchairs may be necessary, depending on the stage of the disease.
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Occupational therapy and adaptations at home and in daily routines can be helpful. Examples include:
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Installing grab bars in hallways and bathrooms
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Using a shower chair
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Installing night lighting
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Repositioning furniture to facilitate mobility
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Removing rugs to prevent tripping
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Using cups with lids and straws
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Choosing non-slip, easy-to-wear footwear
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Rest whenever needed, and prioritize high-quality nighttime sleep. If sleep difficulties arise, consult your physician — some medications (e.g., cannabidiol oil) may help.
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Maintain a healthy diet and ensure adequate hydration.
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Some patients may benefit from supplements such as Coenzyme Q10, vitamin D, or vitamin B12. These should only be taken under medical supervision — do not self-prescribe vitamins or dietary supplements.
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Weight control is important to avoid further mobility challenges.
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For diplopia (double vision) caused by ataxia, prism glasses may help. For nystagmus, medications may be beneficial — consult a neuro-ophthalmologist if these symptoms appear.
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For dysarthria (speech difficulties), speech therapy is recommended. In advanced stages, consider assistive communication devices (available for smartphones, computers, tablets, etc.).
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For dysphagia (difficulty swallowing), especially in later stages of the disease, it is highly recommended to see a speech-language pathologist. There are exercises that can improve swallowing and reduce the risk of choking and aspiration pneumonia.
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Avoid stress as much as possible, as it generally worsens ataxia symptoms.
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If necessary, medications are available for managing anxiety and depression. Talk to your doctor to find the most appropriate options.
Note: Some patients with various types of cerebellar ataxia report symptom relief following neuromodulation or non-invasive cerebellar stimulation therapies, such as transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS), when performed by certified physiotherapists. However, even though these therapies are already available commercially, they have not yet been approved by the FDA (United States) or ANVISA (Brazil) for the treatment of ataxias — meaning they are considered experimental and without guaranteed efficacy.
See information about medications for ataxia symptoms.
See information about treatments and care for patients.
See information about those with a recent diagnosis.
See information about Support Groups for patients and caregivers.
10. REFERENCES
The references below include academic sources and specialized organizations that supported the information in this fact sheet, including peer-reviewed articles, genetic repositories (OMIM), literature summaries (GeneReviews), and informational materials from ataxia foundations. For more information, see the ataxia.info References list .
Ref #1
Source:
NAF (National Ataxia Foundation)
Copyright © National Ataxia Foundation
Language:
English
Date:
Revised 11/2018
Ref #2
Source:
GARD - Genetic and Rare Diseases Information Center.
Copyright © National Center for Advancing Translational Sciences - National Institutes of Health (NIH).
Language:
English
Date:
Last Updated: January 2024
Ref #3
Source:
NEUROMUSCULAR DISEASE CENTER (Alan Pestronk, MD)
Washington University, St. Louis, MO - USA
Language:
English
Date:
Last Updated: Please see https://neuromuscular.wustl.edu/rev.htm
Ref #4
Source:
Dr. Marija Cvetanovic
YouTube - Copyright © National Ataxia Foundation (NAF)
Language:
English
Date:
Nov 7, 2023
Ref #5
Source:
Puneet Opal, MD, PhD and Tetsuo Ashizawa, MD
Copyright © GeneReviews. GeneReviews ® is a registered trademark of the University of Washington, Seattle.
Language:
English
Date:
Last Updated: February 2, 2023
Ref #6
Source:
OMIM ® - An Online Catalog of Human Genes and Genetic Disorders.
Copyright © Johns Hopkins University.
Language:
English
Date:
Edit History: alopez: 11/29/2023
Ref #7
Source:
Presented by: Dr. Sharan Srinivasan
YouTube - Copyright © National Ataxia Foundation (NAF)
Language:
English. You can enable subtitles and configure automatic translation of subtitles into other languages.
Date:
May 8, 2023
Ref #8
Source:
Presented by: Dr. James Orengo
YouTube - Copyright © National Ataxia Foundation (NAF)
Language:
English. You can enable subtitles and configure automatic translation of subtitles into other languages.
Date:
May 25, 2023
Ref #9
Source:
Tetsuo Ashizawa et al
Copyright © PubMed Central
Language:
English.
Date:
Nov 13, 2013
Ref #10
Source:
Huda Y Zoghbi, Harry T Orr
Copyright © PubMed Central
Language:
English.
Date:
Mar 20, 2009