SCA7 Fact Sheet
Ataxia:
SCA7 (Spinocerebellar Ataxia Type 7)
RELATED GENES:
ATXN7
LOCATION:
Chromosome 3 (3p14.1)
MUTATION TYPE:
ATXN7 -> CAG expansion mutation
LAST UPDATE:
April 15, 2025 by Marcio Galvão
HERITAGE:
Autosomal Dominant
Content generated with the support of Generative AI, reviewed by the author.
1. ABOUT SCA7
Spinocerebellar ataxia type 7 (SCA7) is one of a group of inherited disorders of the central nervous system. Like several other inherited ataxias, SCA7 is the result of genetic defects (mutations) that lead to impairment of specific nerve fibers that carry messages to and from the brain, resulting in degeneration of the cerebellum (the brain's coordination center) [1] .
SCA7 is caused by an expansive mutation in the ATXN7 gene, located on chromosome 3p14.1. This mutation consists of the abnormal expansion of repeats of the CAG trinucleotide, which encodes the amino acid glutamine , within the coding region of the gene. As a result, an ataxin-7 protein with an abnormally long glutamine tail is produced, which becomes toxic to neurons. This pathological mechanism classifies SCA7 as one of the polyglutamine expansion diseases (polyQ diseases) [4]. See 7. Additional Information.
Distinctive Clinical Aspects
In addition to classic cerebellar ataxia (coordination dysfunction, dysarthria, and nystagmus), SCA7 presents with progressive retinal degeneration , initially manifesting as loss of central visual acuity (due to macular dystrophy) and progressing to generalized pigmentary retinopathy. This is a hallmark of SCA7 and is related to the fact that the ataxin-7 protein plays an important role in the transcription of proteins by other genes, including retina-specific genes.
More precisely, ataxin-7 is part of the STAGA (SPT3–TAF9–GCN5 acetyltransferase) complex, which is involved in modulating transcription through histone acetylation. Dysfunction of this complex, caused by mutated ataxin-7, contributes to the dysregulation of gene expression in the retina, culminating in retinal degeneration and progressive visual symptoms associated with SCA7 [8] . Visual loss often precedes motor symptoms and is an early diagnostic marker (see 2. Typical Symptoms ). Figure 1 shows a simplified diagram of the pathogenesis of SCA7.
Figure 1 - Simplified pathogenesis of SCA7 - Image generated by the author with the support of Artificial Intelligence
SCA7 illustrates the complexity of genetic neurodegenerative diseases, where alterations in a multifunctional protein (ataxin-7) impact distinct body systems (cerebellum and retina). Advances in understanding its pathophysiology pave the way for gene therapies or reduction of the toxic protein, although effective treatments are not yet available.
Before the molecular identification of the gene causing SCA7, patients with this form of ataxia were often diagnosed with Autosomal Dominant Cerebellar Ataxia Type 2 (ADCA Type II) or ataxia associated with retinitis pigmentosa. Now, with advances in genetic diagnosis, the condition is correctly called spinocerebellar ataxia type 7 (SCA7).
2. TYPICAL SYMPTOMS
Spinocerebellar Ataxia Type 7 (SCA7) is distinguished from most other forms of spinocerebellar ataxia by including, in addition to the typical motor symptoms of ataxia, progressive visual manifestations caused by retinal degeneration [6]. It is important to highlight that clinical presentation can vary significantly among patients—even within the same family—due to factors such as the size of the CAG repeat expansion, age of onset, and epigenetic modifiers. In other words, not all symptoms appear in all individuals, and their severity may range from mild to moderate or severe.
Phenotypic heterogeneity is notable: the presence and severity of symptoms vary among patients, even within the same family, due to factors such as the size of the CAG expansion, age of onset, and epigenetic modifiers [2].
Motor symptoms
(common to other forms of spinocerebellar ataxia):
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Gait ataxia and postural imbalance
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Limb discoordination (appendicular ataxia)
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Abnormal eye movements, including nystagmus and diplopia (double vision)
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Dysarthria (scanning or slurred speech) and dysphagia (difficulty swallowing)
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Muscle rigidity and spasticity in some cases
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Autonomic dysfunctions such as urinary incontinence, bowel constipation, and other symptoms related to degeneration of spinal pathways (hence the term “spinocerebellar”)
Visual symptoms characteristic of SCA7 (not present in other SCAs):
Visual symptoms are caused by progressive retinal dystrophy—more specifically, cone-rod dystrophy—which leads to functional retinal degeneration even when the retina’s morphological appearance is still preserved in early examinations.
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Progressive reduction in visual acuity, which is not correctable with glasses or contact lenses, since the problem originates in the photoreceptor cells of the retina rather than in refractive errors
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In symptomatic SCA7 patients, the retina and optic nerve develop normally but begin to degenerate over time and stop functioning properly
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Central scotomas (dark spots in central vision), which impair tasks such as reading and facial recognition—in other words, peripheral vision may be better than central vision
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Photophobia and difficulty adapting to bright light
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Dyschromatopsia (difficulty perceiving colors), especially in distinguishing between blue and yellow
Notes
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The process of degeneration of the retina and optic nerve occurs in parallel and is partially independent of the motor symptoms of ataxia listed above. For example, some individuals may exhibit mild ataxia symptoms but more severe visual loss, while others may have severe ataxia with only moderate retinopathy.
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In the early stages of the disease, the retina may appear normal during eye exams, even though it is no longer functioning properly. This can be misleading to ophthalmologists. For this reason, evaluation by neuro-ophthalmologists or specialists in hereditary retinal diseases is recommended, given the complexity of differential diagnosis (e.g., ruling out non-SCA7-related retinitis pigmentosa). Specialists may request more specific tests, such as Optical Coherence Tomography (OCT) and Electroretinography (ERG). See Figures 2 and 3 below.
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Visual symptoms affect nearly all SCA7 patients and are initially moderate, but they progress over time. Many patients with SCA7 eventually reach the stage of "legal blindness" under the 20/200 criterion—when the best corrected vision in the better eye is 20/200 or worse, meaning the person can see at 20 feet (6 meters) what a person with normal vision can see at 200 feet (60 meters). This obviously imposes significant limitations on the patient (e.g., inability to drive, read, or recognize faces), impacting quality of life.
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In general, visual symptoms precede the typical motor symptoms of ataxia by several years.
Figure 2 - Normal retina and retina of a patient with SCA7. The light spot is the optic nerve.
Figure 3 - Normal OCT examination and that of a patient with SCA7.
Image Credit: All About SCA7, NAF webinar. Dr. Dr. Ali Hamedani[6]
3. ONSET
According to [3] , the initial signs of SCA7 typically appear in the late teens or early 20s, but the onset of symptoms can range from a few months to over 60 years. This variation is strongly influenced by the number of CAG trinucleotide repeats in the ATXN7 gene. In general, the earlier symptoms appear, the faster the disease progresses.
In SCA7, there is an important correlation between the number of CAG repeats in the ATXN7 gene and the age at which the first symptoms appear, as well as their possible severity [4] .
INFANCY
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The onset of symptoms in childhood (see 4. Anticipation ) is associated with the existence of more than 100 CAG repeats in the ATXN7 gene.
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The Neuromuscular portal [3] reports that above 200 CAG repetitions (generally with paternal inheritance) the onset of symptoms can occur in the first months of life and the course of the disease is usually fatal after two or three years.
ADOLESCENCE
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The onset of symptoms in adolescence or young adults (less than 30 years) is associated with the range between 60 and 100 CAG repeats.
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The initial manifestation is usually visual, with symptoms such as decreased visual acuity, photophobia, and central scotomas, due to cone-rod dystrophy.
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The progression of the disease, although slower than in infantile forms, is still considered accelerated, and can lead to blindness and progressive ataxia in about 10 years.
ADULTS
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In the case of less than 59 CAG repeats, the age at which symptoms appear is generally after 30 years of age.
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Initial symptoms are predominantly cerebellar, such as gait ataxia, dysmetria, and dysarthria, with visual impairment emerging later.
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Clinical progression tends to be slower and, in some cases, less severe than in early-onset forms.
Regardless of age of onset, most patients with SCA7 develop progressive dysarthria, dysphagia, axial and appendicular muscle weakness, and eventually bedridden over the course of the disease. Visual loss is also common in symptomatic forms, although the onset time varies.
Note! Despite the observed correlations, the number of CAG repeats alone does not provide sufficient predictive value for making clinical prognoses about the course of the disease. Other genetic (such as modifier alleles), epigenetic, and environmental factors may influence disease presentation. Therefore, the prognostic value of CAG repeat counts is limited and should be interpreted with caution. See "CAG Expansion Ranges for SCA7" in Section 5. Inheritance .
4. ANTICIPATION
In SCA7, genetic anticipation —that is, earlier and often more severe disease onset in subsequent generations—is a striking phenomenon . This anticipation is attributed to the instability of the CAG repeat expansion in the ATXN7 gene during gametogenesis.
The CAG repeat expansion tends to increase in intergenerational transmission, especially during paternal transmission . Indeed, SCA7 is one of the trinucleotide expansion diseases with the greatest germline instability known, being more prone to large expansions when the mutant allele is inherited from the father [5]. This characteristic can lead to dramatic clinical situations, in which a child presents with severe neurological symptoms years before the parent (or even a grandparent) shows signs of the disease . In these cases, the parent may carry a minor pathogenic expansion—enough to develop symptoms only later in life—while the expansion significantly expands upon transmission to the child, resulting in an early and aggressive form of SCA7.
In SCA7, the number of CAG repeats tends to increase from one generation to the next, with no reported reductions (contractions) in the number of CAG repeats in the transmission of the allele with the mutation from one generation to the next [4] , although in other SCAs this can occasionally occur. This explains the marked anticipation seen in families with SCA7, whose mutation is the most unstable of all diseases caused by abnormal CAG expansions.
5. INHERITANCE
SCA7 is a disease with autosomal dominant inheritance. This means that individuals of both sexes have the same probability of inheriting one copy (allele) of the mutated gene and becoming carriers of the mutation. A child of a person with SCA7 has a 50% chance of inheriting the altered gene (assuming that only one parent—the biological mother or father—is a carrier of the mutation).
Note: It is possible for someone to inherit a gene variant and not develop the disease (i.e., remain asymptomatic), as they may inherit a small mutation in an intermediate range that has low penetrance. However, when the inherited mutation falls within a range considered pathogenic (high penetrance), the disease will manifest at some point in life.
CAG Expansion Ranges for SCA7
Each person has two copies of the ATXN7 gene—one inherited from the mother and the other from the father. One allele may have, for example, 14 CAG repeats, which is normal and does not cause disease, while the other allele (the second copy of the same gene) may have, for instance, 72 repeats—in which case the person will develop the disease sooner or later.
The CAG repeat thresholds used for the genetic diagnosis of SCA7 are listed below [4]:
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Normal Range – 7 to 27 CAG repeats: Does not lead to disease. Alleles with ≤27 repeats are stable across generations.
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Intermediate Range – 28 to 33 CAG repeats: Uncertain penetrance. Some individuals may remain asymptomatic throughout life; others may develop very mild symptoms. Germline instability may occur.
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Pathogenic Range: Whether or not the disease manifests depends on the penetrance associated with the specific sub-ranges:
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Pathogenic with reduced penetrance – 34 to 36 CAG repeats: Increased risk for developing SCA7, but not all carriers will show symptoms. Penetrance is incomplete.
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Pathogenic with full penetrance – 37 or more CAG repeats: In this range, 100% of carriers develop the disease, with severity and age of onset correlated to the size of the expansion.
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Note: "Autosomal" means that the gene is located on any chromosome except the sex chromosomes X and Y. Genes, like chromosomes, typically exist in pairs (we have a pair of each gene—one copy 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 enough to transmit a physical trait (such as dimples in the cheeks) or a genetic disease (such as hereditary ataxias) from one generation (parents) to the next (children).
Figure 4 – Source: MedlinePlus, U.S. National Library of Medicine.
6. PREVALENCE
Spinocerebellar Ataxia Type 7 (SCA7) is a relatively rare form of autosomal dominant ataxia. The estimated global prevalence is less than 1 case per 300,000 people , making it less common than other subtypes such as SCA1, SCA2, SCA3 (Machado-Joseph), and SCA6. It represents on average 2% to 5% of all diagnosed cases of spinocerebellar ataxias worldwide, although this proportion varies significantly depending on the population studied [7] .
SCA7 occurs predominantly in two racial population groups: Northern Europeans and Africans.
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SCA7 is notably prevalent in certain populations in Sweden, Finland, Mexico, and South Africa.
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In Mexico, in certain regions (e.g., Durango), SCA7 accounts for ~85% of autosomal dominant SCAs, likely due to reproductive isolation and high consanguinity.
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Other regions with a more moderate prevalence are the United States (Afro-descendants), France and Germany.
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SCA7 is the only expansion repeat disease (other than Huntington's disease type 2 (HDL2) that affects a significant number of individuals of African ancestry . For this reason, a substantial fraction of individuals with SCA7 in the United States are of African descent.
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In Asia (in countries such as China, Japan, South Korea and India) and the Middle East, SCA7 is rare (<1% of SCAs).
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The rarity of SCA7 in some regions of the world can be partially explained by evolutionary and genetic factors, especially negative selection against highly expanded CAG alleles in the ATXN7 gene.
7. ADDITIONAL INFORMATION
SCA7 ataxia is one of the "polyglutamine diseases" (PolyQ). It occurs when the allele (copy) of the ATXN7 gene inherited from one of the parents contains a mutation with an abnormally high number of CAG trinucleotide repeats (Cytosine, Adenine, Guanine), which code for the amino acid glutamine (Q) in the resulting protein. This leads the protein encoded by the mutant gene to have an abnormal structure, with an excessive stretch of glutamines. This abnormal protein tends to accumulate and form aggregates, especially within the nuclei of nerve cells (neurons).
Nature has protective mechanisms to “clean up” cells by degrading “problematic” or “unnecessary” proteins. However, for some reason, these mechanisms do not work well on polyglutamine aggregates, which are insoluble by natural means. As a result, these defective proteins become toxic and may disrupt vital cellular processes such as autophagy, DNA transcription, axonal transport, and protein homeostasis, ultimately leading to degeneration and death of neurons in the cerebellum (as well as other nervous system cells). The symptoms of ataxia arise from this neuronal loss.
Additional notes on PolyQ disorders
(Adapted from "Pathogenesis of SCA3 and implications for other polyglutamine diseases," Hayley S. McLoughlin et al., 2020)
1. Currently, nine PolyQ disorders are known, including Huntington's Disease (HD), Dentatorubral-pallidoluysian atrophy (DRPLA), Spinal and Bulbar Muscular Atrophy (SBMA), and six types of spinocerebellar ataxias (SCAs)—namely SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17. All of these diseases result from expanded CAG repeats within coding regions of their respective genes and share several common features. For example, all PolyQ diseases are autosomal dominant (except for SBMA, which is X-linked), primarily affect the central nervous system (CNS)—although peripheral nerves and muscles can also be involved—and progress over the course of years. Additionally, there is an inverse correlation between the size of the mutation (number of CAG repeats) and the onset and severity of symptoms, and a phenomenon known as anticipation may occur (where the disease appears earlier and more severely in subsequent generations).
2. In PolyQ diseases, misfolded proteins with excessive glutamine (CAG repeats) tend to aggregate, mainly in the nuclei of neurons, though aggregates may also form in the cytosol (cytoplasm) and even in distal axons. The exact role of these nuclear aggregates is still unclear, but one hypothesis is that they may initially be protective (neuroprotective), later becoming toxic (pathogenic) to nerve cells. These aggregates may sequester essential proteins such as transcription factors, and damage critical components such as mitochondria, the chaperone system (which helps fold proteins correctly), the ubiquitin-proteasome system (UPS) (which degrades unwanted or damaged proteins), and interfere with autophagy, the cell’s “quality control” process for protein turnover. Even DNA repair mechanisms in the nucleus may be affected. These impairments compromise normal neuronal function and may lead to neuronal death.
3. Other cell types, including glial cells (such as astrocytes, microglia, and oligodendrocytes), may also play important roles in the pathogenesis of spinocerebellar ataxias and other PolyQ disorders. For instance, glial cells (Bergmann glia) have been shown to contribute to the neurodegenerative process in SCA7, and glial alterations observed in animal models of SCA1 and Huntington’s disease may represent a shared mechanism across other PolyQ diseases.
Note: Recent studies suggest that DNA damage is directly associated with neuronal loss (neuron death) in SCA7 ataxia. Researchers have found that the mutation in the ataxin-7 protein (produced by the ATXN7 gene) is enough to cause DNA damage in nerve cells, and conversely, that some DNA repair processes are impaired due to the mutant protein in SCA7. For more details, see the SCASource article listed in section 10. References.
Diagnosis – SCA7 can be diagnosed with molecular genetic testing (DNA testing) to detect mutations (abnormal CAG repeat expansions) in the ATXN7 gene. This is especially recommended if there is already a confirmed case in the family (i.e., positive family history of SCA7). Before ordering genetic tests, a neurologist typically conducts neurological examinations to assess symptoms, reflexes, and eye abnormalities, as well as reviewing family history. Imaging tests may also be ordered to check for cerebellar atrophy or visual problems, which are common in SCA7.
Note: Although genetic testing can be challenging, time-consuming, and expensive, it is important because it enables better genetic counseling for family members (regarding inheritance risk), allows more precise disease management, and provides access to clinical trials for specific ataxia treatments.
8. THERAPIES AND DRUGS BEING TRIALED FOR THIS ATAXIA
View NAF Treatment Pipeline for SCA7
Natural History of Spinocerebellar Ataxia Type 7 (SCA7) - ClinicalTrials.gov ID NCT02741440
A Natural History Study for SCA7 has been ongoing in the United States since 2016 [9] , and in May 2023, recruitment began for additional patients aged 12 and older. The study is expected to end in December 2028. During this period, patients will be closely monitored by researchers. The goal is to collect data on the neurological and vision problems that can occur in SCA7. Researchers want to understand what changes occur in the eyes and brains of patients with SCA7, and how the disease progresses. This information is extremely valuable for disease management and for research into therapies and medications for SCA7. The principal investigator is Dr. Laryssa A. Huryn of the National Eye Institute (NEI). The study is being conducted in Maryland, USA.
It's important for patients with ataxias in general, and SCA7 in particular, to stay up-to-date on ongoing research and seek clinical trials if they have the opportunity. There is some promising gene therapy research underway, conducted both by researchers interested in cures for SCA7 ataxia (in the field of neurology) and in the field of ophthalmology in general, where it is even more advanced (some gene therapies already exist for certain types of retinal diseases).
About ASO gene therapies
Learn More - Snapshot: What is an antisense oligonucleotide (ASO/AON)? NAF SCASource.
9. TREATMENTS
SCA7 ataxia currently has no cure, but it is possible to treat symptoms to improve quality of life and provide continuous support to the patient. It is important that patients with SCA7 be followed by a neurologist and a specialized multidisciplinary medical team, with the gradual inclusion of additional healthcare professionals as needed, depending on symptom progression (such as a geneticist, neuro-ophthalmologist, neurofunctional physical therapist, occupational therapist, speech-language pathologist, nutritionist, etc.).
Below are some general recommendations for managing ataxia symptoms in SCA7:
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Neurofunctional physiotherapy, exercise (especially stationary cycling), and other regular physical activities (such as Yoga, Pilates, water aerobics, etc.) are recommended—according to each person’s abilities.
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To reduce the risk of falls due to balance issues while walking, assistive devices like canes, walkers, or wheelchairs may be used, depending on the stage of the disease.
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Occupational therapy and some home and lifestyle adaptations can help (e.g., installing grab bars in hallways and bathrooms, using a shower chair, placing night lights, rearranging furniture to improve mobility, removing rugs to prevent tripping, using lidded cups with straws, wearing shoes with non-slip soles that are easy to put on, etc.).
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Rest as needed, and maintain good-quality nighttime sleep. In case of sleep difficulties, consult a physician—some medications (e.g., cannabidiol oil) may help.
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Maintain a healthy diet and good hydration.
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Supplements and vitamins may be recommended—consult a physician to evaluate necessity. Do not take supplements without medical supervision.
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Weight control is advisable to avoid further mobility challenges.
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For dysarthria (speech difficulties), if it occurs, specialized speech therapy (speech-language pathology) is recommended. Depending on the stage, assistive communication devices (for smartphones, computers, iPads, etc.) may be considered.
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For dysphagia (swallowing difficulties), which may appear in more advanced stages, a consultation with a speech-language pathologist is also recommended. Specific exercises can aid swallowing and reduce the risk of choking that may lead to aspiration pneumonia.
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Avoid stress as much as possible, as it tends to worsen ataxia symptoms.
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If needed, medications for anxiety and depression are available. Consult a physician to evaluate the most appropriate options.
For visual symptoms:
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Consult a neuro-ophthalmologist or retina specialist annually to monitor visual symptoms caused by SCA7. While there is still no cure for the specific visual problems caused by SCA7, it is important to check for other treatable visual conditions (e.g., cataracts, glaucoma). The neuro-ophthalmologist may also prescribe vitamin supplements with potential neuroprotective effects.
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Optometrists specialized in low vision rehabilitation can also provide helpful guidance to improve quality of life.
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Patients with SCA7 may also benefit from joining support groups for people with visual impairment, where they can exchange experiences and receive advice for managing daily visual challenges.
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Assistive devices (hardware and software) for people with visual impairments may also help—such as AI-powered apps that convert text to speech for automatic reading, or voice-to-text for communication.
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Other resources include guide dogs and learning tactile writing systems such as Braille.
Note: Some patients with different types of cerebellar ataxias report benefits and symptom improvement after neuromodulation sessions or non-invasive cerebellar stimulation—such as transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) with certified physiotherapists. However, it is important to note that although this therapy is already being offered commercially, it has not yet been approved by the FDA in the United States (or by ANVISA in Brazil) for the treatment of ataxias—meaning it remains experimental and without guaranteed results.
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 NAF - 01/2019
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:
Albert R. La Spada, MD, PhD.
Copyright © GeneReviews. GeneReviews is a registered trademark of the University of Washington, Seattle.
Language:
English
Date:
Last Update: July 23, 2020.
Ref #5
Source:
OMIM® - An Online Catalog of Human Genes and Genetic Disorders.
Copyright © Johns Hopkins University.
Language:
English
Date:
Edit History: terry: 12/22/2010
Ref #6
Source:
Presented by: Dr. Ali Hamedani
YouTube - Copyright ® National Ataxia Foundation (NAF)
Language:
English. You can enable subtitles and configure automatic translation of subtitles into other languages.
Date:
Sep 6, 2023
Ref #7
Source:
Presented by: Dr. Colleen Stoyas
YouTube - Copyright ® National Ataxia Foundation (NAF)
Language:
English. You can enable subtitles and configure automatic translation of subtitles into other languages.
Date:
Sep 20, 2023
Ref #8
Source:
Written By Dr Hannah K Shorrock. Edited by Dr. Celeste Suart
SCASource article. Copyright ® National Ataxia Foundation (NAF)
Language:
English. You can enable subtitles and configure automatic translation of subtitles into other languages.
Date:
September 15, 2023
Ref #9
Source:
ClinicalTrials.gov - ID NCT02741440
Sponsor National Eye Institute (NEI)
Language:
English.
Date:
Study Completion (Estimated): 2028-12-31