SCA10 Fact Sheet
Ataxia:
SCA10 (Spinocerebellar Ataxia Type 10)
RELATED GENES:
ATXN10
LOCATION:
Chromosome 2 2 (22q13.31)
MUTATION TYPE:
ATXN10 -> Intronic mutation by ATTCT expansions
HERITAGE:
Autosomal Dominant
LAST UPDATE:
April 30, 2025 by Marcio Galvão
Content generated with the support of Generative AI, reviewed by the author.
1. ABOUT SCA10
Spinocerebellar Ataxia Type 10 (SCA10) is a specific form of hereditary ataxia within the group of spinocerebellar ataxias — a set of neurodegenerative diseases that primarily affect the cerebellum and its connections. In SCA10, genetic alterations interfere with the function of nerve fibers responsible for conducting signals between the brain and the rest of the body, leading to the progressive degeneration of the cerebellum — a structure essential for fine motor coordination and balance [1].
SCA10 is caused by an abnormal expansion of ATTCT pentanucleotide repeats in an intronic region of the ATXN10 gene, located on chromosome 22 (22q13.31). This mutation was first identified in Mexican populations and later in groups from southern Brazil, suggesting a possible regional founder effect. In pathogenic cases, the number of abnormal ATTCT repeats may exceed 4,500, whereas healthy individuals typically have fewer than 32 repeats (see Section 5: Inheritance). The exact origin of these expanded repeats remains unknown [8].
SCA10 was the first human genetic disease discovered to be caused by an intronic pentanucleotide repeat expansion. Since the identification of the SCA10 mutation, several other diseases have been reported to result from intronic pentanucleotide expansions, including other forms of ataxia (see Section 7: Additional Information).
Although the exact pathogenic mechanism of the SCA10 mutation is not yet fully understood, evidence suggests that RNA containing expanded repeats may form abnormal structures that disrupt cellular function — a possible case of RNA-mediated toxicity. One hypothesis [8] proposes that the large number of nucleotide repeats interferes with RNA splicing, affecting the stability of messenger RNA (mRNA) responsible for protein synthesis. In SCA10, even though the expansion occurs in a non-coding region, it is plausible that the excessive repeats produce toxic RNA. This toxic RNA may lead to cellular dysfunction and trigger apoptosis — a form of programmed cell death that occurs in a controlled manner in the body. This process (illustrated in Figure 1) may lead to the death of neurons in the cerebellum, resulting in the neurodegenerative symptoms associated with ataxia.
Figure 1 provides a simplified illustration of SCA10 pathogenesis (image generated by the author with AI support).
2. TYPICAL SYMPTOMS
The clinical phenotype of SCA10 is variable, even within the same family, suggesting that genetic or environmental modifying factors may influence the clinical expression of the disease. Some people may develop more symptoms than others, and when they do occur, symptoms can be mild, moderate, or severe. The following list is for reference only.
Symptoms of SCA10 [1, 3, 4]
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Typically, problems with balance and coordination, typical of cerebellar ataxias, are first noticed. The affected person has difficulty walking, and this difficulty gradually worsens, increasing the risk of falls, which become more frequent. Over time, the use of a cane, walker, and eventually a wheelchair may become necessary.
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Over time, dysarthria (slurred speech) may develop due to impaired muscle coordination involved in speech production. Nystagmus, characterized by involuntary and repetitive eye movements, may also occur.
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Also, after a few years, hand and arm coordination becomes more compromised. Fine motor skills like handwriting and buttoning clothes are affected first, and eventually, basic daily tasks like feeding and dressing become more difficult.
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In the later stages of the disease, difficulty swallowing (dysphagia) may occur as a result of the inability to control the muscles of the mouth and throat during eating, and aspiration pneumonia can become a significant life-threatening condition.
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A notable aspect of SCA10, which distinguishes it from other spinocerebellar ataxias, is the possible occurrence of epileptic seizures (convulsions). The prevalence of epilepsy varies between 20% and 80%, depending on the cohort analyzed: it is more frequent in Mexican families and less common in Brazilian patients, suggesting a genetic or epigenetic influence. Seizures usually manifest years after the onset of ataxia.
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Some individuals with SCA10 may experience additional symptoms such as mild cognitive impairment, mood disorders (such as depression, anxiety, apathy, irritability), sensory peripheral neuropathy with numbness or paresthesias in the hands and feet, and pyramidal signs such as exaggerated active reflexes (hyperreflexia), and/or Babinski plantar reflex signs (when the sole of the foot is tickled, the big toe reflex is upward instead of downward).
Magnetic resonance imaging (MRI) scans may indicate cerebellar atrophy (Figure 2) due to the death of neurons (Purkinje cells). This would be the main cerebellar pathology in SCA10 [7] .
Figure 2 - Magnetic resonance imaging showing cerebellar atrophy in SCA10 due to loss of Purkinje cells
3. ONSET
There are recorded cases of the onset of symptoms of SCA10 between 12 and 83 years of age, although most patients present the first clinical signs in young adulthood or middle age. Population studies indicate a mean age of onset of around 33.9 ± 9.8 years [6] , with variations observed between different ethnic groups and families. Data from Brazilian and Mexican cohorts show onset ranges between 10 and 40 years , but with sporadic records outside this window.
Juvenile cases (≤ 20 years) are rare (< 5%), associated with very large expansions (> 2,000 ATTCT repeats) and maternal transmission (Ashizawa et al., 2023).
SCA10 progresses slowly, meaning symptoms develop gradually over several years. The rate of progression can vary substantially between patients, even within a family, suggesting the involvement of genetic or environmental modifying factors.
Although many individuals with SCA10 can maintain functional independence for several years after the onset of symptoms, life expectancy may be reduced due to complications associated with disease progression. For example, severe seizures can be fatal if not adequately controlled [4] .
4. ANTICIPATION
Anticipation (earlier onset of symptoms) in SCA10 is directly associated with the unstable expansion of the ATTCT pentanucleotide in the ATXN10 gene. In successive generations, expanded alleles (>800 repeats) tend to increase in size , especially when paternally transmitted , resulting in earlier onset and increasing severity of symptoms [4] .
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Paternal transmission is linked to greater instability in the number of ATTCT repeats, with reports of expansions of up to 4,500 repeats , while maternal transmission shows relative stability.
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Some paternal transmissions can cause a reduction (contraction) in the number of repeats in the allele, rather than an increase (expansion). This phenomenon is rare, but it highlights the complexity of repeat dynamics.
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Anticipation of SCA10 has been suggested in some Brazilian families; however, further studies are needed to confirm this observation [Teive et al 2004].
Note - The Neuromuscular portal [3] reports that the onset of symptoms may be brought forward by up to 20 years between generations, especially with paternal transmission.
5. INHERITANCE
SCA10 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 SCA10 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 is important to note that a person may inherit a gene variant without developing the disease (i.e., remain asymptomatic), especially if the mutation 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.
Repeat Expansion Ranges for SCA10
The diagnostic thresholds for ATTCT repeat expansions in the ATXN10 gene are summarized below:
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Normal range (non-pathogenic): 10 to 32 ATTCT repeats
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Intermediate range (typically asymptomatic): 33 to 279 ATTCT repeats
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Reduced penetrance (more than half of carriers develop symptoms): 280 to 799 ATTCT repeats
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Full penetrance (100% of carriers develop symptoms): 800 to 4,500 ATTCT repeats
Notes:
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The ranges reported in sources [4] and [6] differ slightly. The recent reclassification of the pathogenic threshold to ≥800 repeats (instead of 850) is discussed in studies published between 2022 and 2025.
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Alleles with 280–799 repeats require caution: some paternal transmissions have resulted in expansions beyond 800 repeats.
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The presence of interruptions in the ATTCT sequence (e.g., ATTCC insertions) may modulate symptom severity and penetrance, affecting case identification. See Section 7: Additional Information.
Sources: Peer-reviewed articles (2022–2025) [12, 13, 14] discussing the genetic criteria for SCA10. Each range above is based on consensus from these publications.
Note: "Autosomal" means that the gene is located on any chromosome except the sex chromosomes X and Y. Genes, like chromosomes, usually come in pairs (we have one copy of each gene inherited from the mother and one from the father). "Dominant" means that only one copy of the responsible gene (one allele) inherited from either the mother or the father is sufficient to transmit a physical trait (such as having dimples) or a genetic disorder (such as hereditary ataxias) from one generation (parents) to the next (children).
Figure 3 – Source: MedlinePlus, U.S. National Library of Medicine.
6. PREVALENCE
SCA10 is considered a rare disease, with unknown global prevalence due to its concentration in specific populations and the lack of comprehensive epidemiological studies. It is most prevalent in Latin American populations, particularly in Mexico and Brazil, where it is the second most common hereditary ataxia in some regions. For example, in southern Brazilian states such as Paraná and Santa Catarina, SCA10 is the second most frequent spinocerebellar ataxia, second only to SCA3 [11].
According to source [6], the first SCA10 cases were identified in Latin American countries, with isolated cases also reported in the United States, China, and Japan. One hypothesis suggests that the mutation migrated from East Asia to North America via the Bering Strait, reaching the ancestral Native American population and later spreading to South America. A case of SCA10 was reported in an individual of Sioux Native American descent.
7. ADDITIONAL INFORMATION
Mutations in Non-Coding Regions
Introns are non-coding segments of DNA—these parts of the genetic code do not synthesize proteins. During the splicing process, which occurs during the synthesis of messenger RNA (mRNA), introns are removed, resulting in an mRNA strand containing only exons, which are the protein-coding regions. Genes can contain mutations (such as expanded repeats of nucleotide sequences) in both introns and exons.
In addition to occurring in coding or non-coding regions of different genes, expanded nucleotide repeats can consist of tri-, penta-, hexa-, or even dodeca-nucleotide sequences. For example:
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In Spinocerebellar Ataxia Type 3 (SCA3), the expanded repeat is the trinucleotide CAG (cytosine-adenine-guanine), which codes for the amino acid glutamine, and occurs in the exon (coding region) of the ATXN3 gene.
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In Spinocerebellar Ataxia Type 12 (SCA12), the expansion is also CAG, but it occurs in an intron of the PPP2R2B gene.
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In Friedreich's Ataxia, the expansion involves the trinucleotide GAA (guanine-adenine-adenine), located in an intron of the FXN gene.
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In Spinocerebellar Ataxia Type 10 (SCA10), our current focus, the expansion is the pentanucleotide ATTCT (adenine-thymine-thymine-cytosine-thymine), located in an intron of the ATXN10 gene.
Beyond SCA10, the following examples [8] show other ataxias also caused by intronic pentanucleotide expansions:
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Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome (CANVAS) is caused by an AAGGG pentanucleotide expansion in an intron of the RFC1 gene.
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Spinocerebellar Ataxia Type 31 (SCA31) is caused by a TGGAA expansion in the introns of the BEAN1/TK2 genes.
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Spinocerebellar Ataxia Type 37 (SCA37) is caused by a TTTCA expansion in an intron of the DAB1 gene.
When mutations occur within coding regions (exons), the synthesis of the protein encoded by the gene is directly affected, potentially resulting in misfolded proteins that have toxic effects on the cells where they are produced. However, the presence of expanded nucleotide repeat mutations in non-coding regions of genes can also cause genetic diseases, including the various types of ataxias listed above.
Interruptions in ATTCT Repeats
Within a series of ATTCT pentanucleotide repeats in the ATXN10 gene, interruptions or variations in the sequence may occur. These interruptions can include different sequences, such as ATTTTCT and ATATTCT. These variations act as genetic modifiers that can influence the penetrance and severity of the disease symptoms, potentially increasing or decreasing the likelihood that a carrier will develop specific symptoms. Source [8] notes that interruptions in the ATTCT repeat sequence may be a significant risk factor for the development of epileptic phenotypes (seizures) in SCA10. Conversely, pure ATTCT expansions (without interruptions) have been associated in some cases with Parkinsonian symptoms. These observations highlight that the relationship between symptoms and repeat structure in SCA10 is complex and not yet fully understood.
Diagnosis of SCA10
SCA10 can be diagnosed by identifying expanded ATTCT pentanucleotide repeats in the ATXN10 gene through molecular genetic testing (DNA analysis).
Limitations of Genetic Testing
If the test shows that the number of ATTCT repeats in both inherited ATXN10 alleles falls within the normal range, a negative diagnosis is conclusive, and SCA10 can be ruled out. However, if the number of repeats falls into a range involving long repeat sequences, more sophisticated genetic tests may be necessary for accurate identification of the mutation’s size and composition. Current diagnostic methods using PCR or Southern blotting may not precisely resolve the genomic structure when large repeat expansions are present—such as the hundreds (or even thousands) of ATTCT repeats found in SCA10. However, as noted in [6], modern technologies such as Single Molecule, Real-Time (SMRT) sequencing from PacBio and high-resolution Optical Genome Mapping from BioNano Genomics enable precise sizing and analysis of the ATTCT repeat. This detailed information is clinically important for both disease management and genetic counseling, as repeat structure may influence disease penetrance, symptoms, and progression.
Prenatal Genetic Testing - Once an expanded ATTCT repeat in the ATXN10 gene is identified in a family member through m olecular genetic testing, there is a 50% chance that the mutation may be passed on to their children. For this reason, prenatal testing during pregnancy can be considered to determine whether the embryo carries the mutation that may cause the disease. This is an ethically sensitive topic, involving personal and family decisions. Individuals at risk are encouraged to discuss with their partners and seek genetic counseling to make well-informed decisions.
8. THERAPIES AND DRUGS IN TRIALS FOR SCA10
9. TREATMENTS
SCA10 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 for individuals with SCA10 to be followed by a neurologist and a specialized multidisciplinary medical team. Additional healthcare professionals should be included gradually as needed based on the patient’s symptoms (e.g., geneticist, neuro-ophthalmologist, neurofunctional physical therapist, occupational therapist, speech therapist, nutritionist, etc.).
The primary focus of SCA10 treatment is seizure control, as uncontrolled seizures can lead to a fatal epileptic state. Conventional anticonvulsants such as Levetiracetam, Phenytoin, Carbamazepine, and Valproic Acid provide reasonable seizure control, although occasional seizures may still occur even under medication [4].
In addition to anticonvulsant medications for patients experiencing seizures, the following are recommended:
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Neurofunctional physiotherapy and other regular physical activities are encouraged (as tolerated by the patient).
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To reduce the risk of falls due to balance difficulties while walking, canes, walkers, or wheelchairs may be used depending on disease progression.
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Occupational therapy and some home adaptations can help, such as:
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Installing grab bars in hallways and bathrooms
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Using shower chairs
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Adding night lighting
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Repositioning furniture to facilitate movement
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Removing rugs to prevent tripping
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Using cups with lids and straws
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Choosing shoes with non-slip soles and easy fastening.
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Resting whenever needed and ensuring good quality sleep is important. In case of sleep difficulties, consult a physician, as some medications—such as Cannabidiol oil—may help.
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Maintaining a healthy diet and good hydration.
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Supplements such as Coenzyme Q10, and vitamins (D, B12, etc.) may be recommended—only under medical supervision.
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Weight management is advised to avoid worsening mobility issues.
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For nystagmus, medications may help. A neuro-ophthalmologist should be consulted if this symptom appears.
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For dysarthria (speech difficulties), speech therapy is recommended. Depending on the disease stage, assistive communication devices (smartphones, computers, tablets) may be considered.
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In case of dysphagia (swallowing difficulties) in advanced stages, speech-language pathology is also recommended—there are exercises that may improve swallowing and reduce the risk of aspiration pneumonia.
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Avoiding stress as much as possible, as it often worsens ataxia symptoms.
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If necessary, there are medications available for anxiety and depression. A physician should be consulted to assess the most appropriate options.
Note: Some patients with various forms of cerebellar ataxia report benefits and symptom improvement after undergoing neuromodulation or non-invasive cerebellar stimulation, such as transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) with certified physical therapists. However, although this therapy is commercially available, it has not yet been approved by the FDA (U.S.) or ANVISA (Brazil) for the treatment of ataxias—meaning it remains an experimental approach without guaranteed outcomes.
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 12/2018
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: November 2023
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:
Tohru Matsuura, MD and Tetsuo Ashizawa, MD. NLM - GeneReviews © 1993-2019.
Copyright © GeneReviews is a registered trademark of the University of Washington, Seattle.
Language:
English
Date:
Last Update: September 19, 2019.
Ref #5
Source:
OMIM® - An Online Catalog of Human Genes and Genetic Disorders.
Copyright © Johns Hopkins University.
Language:
English
Date:
Edit History: alopez: 12/15/2023
Ref #6
Source:
Presented by: Dr. Birgitt Schuele at 2020 PacBio Neuroscience Day
YouTube - PacBio
Language:
English. You can enable subtitles and configure automatic translation of subtitles into other languages.
Date:
Jun 15, 2021
Ref #7
Source:
Guangbin Xia, MD, PhD et al
Copyright ® PMC - PubMed Central - Epub 2013 Jun 29. PMID: 23813740; PMCID: PMC3923576.
Language:
English
Date:
Published online 2013 Jun 29
Ref #8
Source:
Kurosaki T, Ashizawa T.
Copyright ® PMC - PubMed Central - PMID: 36199580; PMCID: PMC9528567.
Language:
English
Date:
Published online 2022 Sep 15
Ref #9
Source:
Dr. Mario Cornejo-Olivas
NAF (National Ataxia Foundation) Webinar on YouTube
Language:
English
Date:
Published in November 2024
Ref #10
Source:
Dr. Birgitt Schüle
NAF (National Ataxia Foundation) Webinar on YouTube
Language:
English
Date:
Published in November 2024
Ref #11
Source:
Hélio A Ghizoni Teive et al
Copyright ® PMC - PubMed Central - PMID: 40232546
Language:
English
Date:
Published in April 2025
Ref #12
Source:
C Alejandra Morato Torres et al
Copyright ® PMC - PubMed Central - PMCID: PMC9460507 PMID: 36092952
Language:
English
Date:
Published in August 2022
Ref #13
Source:
Nan Zhang, Tetsuo Ashizawa
Copyright ® PMC - PubMed Central - PMCID: PMC9099484 PMID: 35563872
Language:
English
Data:
Published in May 2022
Ref #14
Source:
Karina Milla-Neyra et al
Copyright ® PMC - PubMed Central
Language:
English
Data:
Published in February 2025