SCA17 Fact Sheet
Ataxia:
SCA17 (Spinocerebellar Ataxia Type 17)
RELATED GENES:
TBP
LOCATION:
Chromosome 6 (6q27)
MUTATION TYPE:
TBP -> Interleaved CAG/CAA Expansion
INHERITANCE:
Autosomal Dominant
LAST UPDATE:
01/05/2025 by Marcio Galvão
Content generated with the support of Generative AI, reviewed by the author.
1. ABOUT SCA10
Spinocerebellar Ataxia Type 17 (SCA17) is a specific form of inherited ataxia within the group of spinocerebellar ataxias, a group of neurodegenerative diseases that preferentially affect the cerebellum and its connections. In SCA17, genetic alterations result in progressive degeneration of the cerebellum — a structure crucial for fine motor coordination and balance, producing symptoms of ataxia.
SCA17 is caused by expansion of the CAG/CAA repetitive sequence in the TATA-box binding protein (TBP) gene, which (briefly) encodes a general RNA transcription factor. The exact pathogenesis is not yet fully understood, but it is believed that the abnormal CAG/CAA polyglutamine expansion in the TBP gene confers a toxic gain-of-function effect , affecting transcriptional (RNA) regulation and producing toxic protein aggregates. These effects cause progressive neuronal dysfunction (especially of cerebellar Purkinje neurons) [1] .
Figure 1 shows in a simplified way the pathogenesis of SCA17 (image generated by the author with AI support).
2. TYPICAL SYMPTOMS
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 SCA17 [1, 2, 3]
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Cerebellar ataxia - difficulty with motor coordination (unsteady gait, trunk and limb ataxia, lack of balance) and dysarthria (slurred speech).
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Cognitive impairment/dementia – loss of recent memory and progressive intellectual decline, with dementia symptoms in advanced stages.
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Psychiatric symptoms – mood swings (depression, anxiety, irritability) and behavioral changes .
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Involuntary movements – chorea (involuntary choreiform movements) and dystonia (abnormal muscle contractions).
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Parkinsonian features – muscle rigidity, bradykinesia and postural instability (extrapyramidal signs) often coexist.
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Pyramidal signs – spasticity and hyperreflexia (corticospinal pathway) may be present.
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Other manifestations – some patients present with seizures (epilepsy and mild ocular manifestations.
Note! SCA17 has also been called “Huntington Disease Type 4” (HDL4) due to its clinical presentation resembling Huntington's disease (progressive chorea with dementia).
MRI scans may indicate cerebellar atrophy due to the death of neurons (Purkinje cells). This would be the main pathology of SCA17, but in addition to the cerebellum, other regions such as the cerebral cortex and brainstem may also undergo degeneration [3].
3. ONSET
SCA17 typically begins in adulthood, with a mean age of onset around the fourth decade of life. Studies report a wide range of clinical onset, ranging from 3 to 55 years , but most patients manifest symptoms between 30 and 50 years of age [1] .
4. ANTICIPATION
Unlike other CAG expansion ataxias, genetic anticipation (increasingly earlier onset in successive generations) is uncommon in SCA17. This is because CAG repeats in TBP are frequently interrupted by CAA codons, which stabilize the sequence during germline transmission and limit further expansion.
In rare families where the CAA interruption is absent (there is only a CAG repeat), instability and anticipation events have been observed, but in general the phenomenon is uncommon [1] .
5. INHERITANCE
SCA17 is an autosomal dominant disease. This means that individuals of both sexes have the same probability of inheriting a copy (allele) of the mutated gene and becoming carriers of the mutation. A child of a person with SCA17 has a 50% chance of inheriting a copy of the altered gene (assuming only one parent is a carrier of the mutation, that is, the biological mother or father).
Note that it is possible for a person to inherit a variant of a gene and not develop the disease (not present symptoms), as they can inherit a small mutation in an intermediate range that has low penetrance . However, when the inherited mutation is in a range considered pathological ( high penetrance ), the disease will manifest itself at some point in life.
Expansion bands for SCA17
The limits of CAG/CAA repeats in the TBP gene for the genetic diagnosis of SCA17 are indicated below in a simplified form [1] :
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Normal Range (does not develop the disease): From 20 to 40 CAG/CAA repeats.
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Intermediate Range (may or may not cause symptoms): 41–48 CAG/CAA repeats.
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Bands with Complete Penetrance (100% of carriers develop symptoms): ≥ 49 contiguous repeats .
Notes:
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Patients with 41 to 44 repeats have variable risk (some remain asymptomatic).
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It was observed that variants in the STUB1 gene can act in conjunction with short expansions of the TBP gene, explaining cases of reduced penetrance – this mechanism involving both genes (TBP and STUB1) was identified in the literature as SCA17-DI (digenic) [1] . See 7. Additional Information .
Note: "Autosomal" means that the gene is located on any chromosome except the X and Y sex chromosomes. Genes, like chromosomes, normally exist in pairs (we have a pair of each gene, one copy of the gene is inherited from the mother, the other from the father). "Dominant" means that just one copy of the responsible gene (an allele) inherited from either the father is enough to pass on a physical characteristic (such as dimpled cheeks) or a genetic disease (such as hereditary ataxia) from one generation (parents) to the next (children).
Figure 2 - Source: MedlinePlus, US National Library of Medicine .
6. PREVALENCE
SCA17 is an extremely rare disease. Fewer than 100 families have been described in the worldwide literature. The global prevalence is estimated to be well below 1 case per 100,000 population . SCA17 represents approximately 0.3% of all cases of autosomal dominant spinocerebellar ataxia [1] .
Note! Some cases are likely underdiagnosed due to clinical overlap with other diseases (e.g., Huntington's disease-like phenotype).
7. ADDITIONAL INFORMATION
Homozygous SCA17: In addition to the classic (dominant) form, extremely rare cases of homozygous SCA17 (in which a person inherits two altered copies of the same gene—one from each father and mother) have been reported. A patient with 47 homozygous repeats in the TBP gene had a late onset of symptoms but a rapid and severe course. Embryo survival was not affected in this case, suggesting that the basic function of TBP is not completely lost even with the homozygous mutation [4] .
Digenic form (SCA17-DI): Individuals with mutations in the TBP gene and the STUB1 gene (digenic co-influence) present an ataxia phenotype similar to SCA17, even with small expansions in the TBP gene. This newly described mechanism may explain clinical variability in affected families.
Clinical overlaps : Due to psychiatric manifestations and chorea, some cases of SCA17 can be confused with Huntington's disease. Therefore, SCA17 is also known as “ Huntington disease–like 4 ” (HDL4) in older descriptions [1] .
Diagnosis of SCA17
Diagnosis of SCA17 requires specific genetic tests that quantify the number of CAG/CAA repeats in the TBP gene. The main tests used are:
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PCR with fragment analysis - Quantifies the total number of CAG/CAA repeats in the TBP gene. This test does not distinguish between pure (CAG only) and mixed (CAG/CAA) repeats, but this is not essential for clinical diagnosis.
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PCR-Repeat Ataxias Panel - Many laboratories offer targeted gene panels for spinocerebellar ataxias, such as SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, DRPLA, and others. In these panels, each expanded gene is tested by individual PCR with specific primers.
Prenatal genetic testing - Once a mutation in the TBP gene has been identified in a family member through molecular genetic testing, there is a 50% chance of passing the mutant allele from that person to their children. Therefore, prenatal testing during pregnancy may be considered to determine whether the embryo carries the mutation that can cause the disease. This is an ethically sensitive issue that involves important personal decisions . People at risk can discuss this with their partners and family members and seek genetic counseling to make better informed decisions.
8. THERAPIES AND DRUGS IN TRIALS FOR SCA17
9. TREATMENTS
SCA17 ataxia currently has no cure, but it is possible to manage symptoms in order to improve quality of life and provide continuous support to the patient. It is important that individuals with SCA17 be followed by a neurologist and a specialized multidisciplinary medical team, with the gradual inclusion of other healthcare professionals as needed based on symptoms (such as a geneticist, neuro-ophthalmologist, neurofunctional physical therapist, occupational therapist, speech-language pathologist, nutritionist, psychiatrist, etc.).
In general, for patients with SCA17, the following practices are recommended:
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Neurofunctional physical therapy and other regular physical activities (according to each individual’s capacity)
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To reduce fall risk due to balance difficulties while walking, canes, walkers, or wheelchairs may be used, depending on disease stage
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Occupational therapy and home/lifestyle adaptations can be helpful, such as:
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Installing grab bars in hallways and bathrooms
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Using a shower chair
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Adding night lighting
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Repositioning furniture to ease movement
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Removing rugs to prevent tripping
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Using cups with lids and straws
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Wearing non-slip, easy-to-wear footwear
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Resting when needed and maintaining good-quality nighttime sleep is essential. In cases of sleep difficulty, consult a physician — certain medications (such as cannabidiol oil) may help
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Maintaining a healthy diet and proper hydration
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Weight control is advisable to avoid worsening mobility issues
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In case of nystagmus, some medications may help. A neuro-ophthalmologist should be consulted if this symptom arises
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If dysarthria (speech difficulties) is present, speech therapy is recommended. Depending on disease stage, assistive communication devices (for smartphones, tablets, computers, etc.) may be considered
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If dysphagia (difficulty swallowing) occurs, especially in later stages, consultation with a speech-language pathologist is advised. Specific exercises can help improve swallowing and reduce the risk of aspiration pneumonia. Nutritional counseling (with a nutritionist) is also recommended
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Avoiding stress as much as possible, as it generally worsens ataxia symptoms
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If needed, medications to manage anxiety and depression are available. Speak with a physician to explore the best options
Note: Some patients with various types of cerebellar ataxias report symptom improvement after undergoing neuromodulation or non-invasive cerebellar stimulation therapies, such as transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) performed by certified physical therapists. However, it is important to note that although these therapies are already being offered commercially, they are still considered experimental and have not been approved by the FDA (United States) or ANVISA (Brazil) for the treatment of ataxias, meaning their efficacy is not guaranteed.
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:
Yasuko Toyoshima et al
© Copyright GeneReviews
Language:
English
Date:
Revised July 28, 2022
Ref #2
Source:
Troels Tolstrup Nielsen et al
Copyright ® PMC - PubMed Central - PMCID: PMC3475097 PMID: 22889412
Language:
English
Date:
Aug, 2012
Ref #3
Source:
Written by Dr. Sriram Jayabal Edited by Dr. Ray Truant
Copyright ® National Ataxia Foundation
Language:
English
Date:
2020
Ref #4
Source:
CH Zühlke et al
Copyright ® Nature - European Journal of Human Genetics
Language:
English
Date:
July 31, 2003
Ref #5
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 #6
Source:
Qiong Liu et al
Copyright ® PMC - PubMed Central - PMID: 31317427 PMCID: PMC6985407
Language:
English
Date:
Last Update: Oct 2019
Ref #7
Source:
OMIM® - An Online Catalog of Human Genes and Genetic Disorders.
Copyright © Johns Hopkins University.
Language:
English
Date:
Edit History: alopez: 06/09/2022