SCA27B Fact Sheet
Ataxia:
SCA27B (Spinocerebellar Ataxia Type 27B)
RELATED GENES:
FGF14
LOCATION:
Chromosome 13 (13q33.1)
MUTATION TYPE:
FGF14 -> GAA repeat expansion (intronic)
HERITAGE:
Autosomal Dominant
LAST UPDATE:
April 18, 2025 by Marcio Galvão
Content generated with the support of Generative AI, reviewed by the author.
1. ABOUT SCA27B
SCA27B (Spinocerebellar Ataxia Type 27B) is a recently identified hereditary form of ataxia. It is a slowly progressive neurodegenerative disease that primarily affects the cerebellum, leading to loss of motor coordination (ataxia). Its genetic cause is a trinucleotide expansion mutation: an abnormal increase in the number of repeats of the GAA sequence in intron 1 of the FGF14 gene, located on chromosome 13 (13q33.1) [1] . This mutation was discovered in 2022 as being responsible for several cases of ataxia previously without a defined genetic diagnosis [2] .
Pathogenesis
Intronic expansion causes haploinsufficiency of the FGF14 gene (partial loss of function), reducing the quantity or function of the FGF14 protein. FGF14 is normally abundant in the cerebellum and modulates the excitability of Purkinje cells (cerebellar neurons responsible for motor control) by interacting with sodium channels in the neurons [3] . Thus, the mutation leads to malfunction of these cerebellar pathways, giving rise to the clinical picture of ataxia. The sodium channel indirectly affected in SCA27B is Nav1.6 , which is encoded by the SCN8A gene.
Note: The FGF14 gene, whose GAA expansion mutation causes SCA27B, does not encode a sodium channel, but rather the FGF14 protein, which modulates the function and expression of voltage-gated sodium channels, particularly Nav1.6. Nav1.6 (sodium channel type 1.6) is highly expressed in cerebellar neurons, especially in Purkinje cells , and is crucial for the repetitive and sustained firing of action potentials. FGF14 interacts directly with Nav1.6, modulating its localization and function in the neuronal membrane. When FGF14 is haploinsufficient, as in SCA27B, this interaction is impaired, leading to dysfunction in neuronal excitability and cerebellar circuitry—which explains the pathophysiological basis of ataxia [4] . See the diagram below.
In the short time since its identification, SCA27B has proven to be one of the most common forms of hereditary late-onset ataxia (ILOCA) , explaining a considerable percentage of cases previously considered idiopathic (without a known cause) [1] .
Figure 1 (generated by the author with the support of Artificial Intelligence) illustrates in a simplified way the pathogenesis of SCA27B .
2. TYPICAL SYMPTOMS
Symptoms of SCA27B primarily involve cerebellar dysfunction and can vary from person to person, even within the same family.
The most common include [3] :
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Gait ataxia: difficulty walking and maintaining balance, resulting in staggering steps and frequent tripping. Progressive gait ataxia occurs in virtually all cases (95–100% of patients).
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Limb incoordination (upper limb ataxia): difficulty performing fine movements with the hands and arms, affecting activities such as writing or picking up objects (present in about 44–71% of cases).
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Speech changes: Cerebellar dysarthria, characterized by slurred or paused speech, occurs in many patients.
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Eye (oculomotor) disorders: Abnormal eye movements, including nystagmus (especially vertical " downbeat " nystagmus) , and difficulty focusing. Cerebellar oculomotor signs occur in up to 80–96% of patients and may also include uncoordinated saccades and gaze nystagmus. Many individuals report double vision (diplopia), blurred/flickering vision (oscillopsia), or a sensation of flickering vision associated with these eye disorders.
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Dizziness and vertigo: The sensation of episodic vertigo or dizziness is common, possibly related to vestibular involvement.
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Tremor and muscle spasms: Some individuals experience mild postural tremor in the hands. Isolated cases have described phenomena such as mild myotonia (difficulty relaxing muscles after contraction) associated with SCA27B, but this is not a typical finding.
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Swallowing difficulties: in more advanced stages, dysphagia (difficulty swallowing) may occur in a smaller number of patients.
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Other less common symptoms: In some cases, mild signs of peripheral neuropathy (e.g., decreased vibration sensitivity in the feet), mild muscle stiffness or spasticity, and autonomic symptoms such as urinary urgency are observed.
It is worth noting that cognitive function is generally preserved in SCA27B – the presence of dementia or significant intellectual deficit is not typical in this condition.
Note! SCA27B may begin with episodes of ataxia— approximately half of patients experience symptoms episodically at disease onset — acute bouts of incoordination that last minutes to days and then temporarily resolve. These episodes can be triggered by intense physical exertion or alcohol or caffeine intake. Over time, episodic attacks tend to give way to a pattern of permanent, continuous ataxia [2, 3] .
3. ONSET
SCA27B is characteristically a late-onset ataxia in adulthood. In most cases, symptoms first appear in middle age or later, with a median age of onset around 60 years [3] . Typically, patients begin to manifest ataxia between the fifth and seventh decades of life (50–70 years).
However, there is considerable variability—rare cases have been described with onset as early as 21–30 years, and, conversely, some asymptomatic individuals as young as 80–90 years who only develop symptoms much later [2, 3] . Even within a family, the age of onset and clinical presentation can vary greatly. In general, once symptoms begin, they progress slowly over the years.
4. ANTICIPATION
Genetic anticipation refers to the phenomenon in which the disease tends to manifest earlier or with greater severity in successive generations. In SCA27B, because it is a repeat expansion mutation, there is instability in the number of GAA repeats from one generation to the next (intergenerational instability), which can lead to some form of anticipation, albeit in a complex manner.
Studies show that FGF14 GAA expansions tend to increase when inherited from the mother (maternal expansion) and, conversely, tend to shrink (contract) when transmitted from the father [3] . This means that if the mother carries the mutation, her children are likely to inherit an allele with an even larger number of repeats , potentially causing them to present symptoms at a younger age or with greater severity (positive anticipation). Conversely, in paternal transmissions, the expanded allele often returns to a smaller size, potentially falling into the reduced or even normal penetrance range. In these cases, the child of an affected father may manifest milder symptoms or even no symptoms at all (which appears to be a generational "skip," as occurs in recessive ataxias, although SCA27B is dominantly inherited).
In summary, there is a possibility of anticipation in SCA27B, but it is not an absolute rule – the severity and age of onset can either increase or, occasionally, regress from one generation to another, depending on the dynamics of repetitions during family transmission.
5. INHERITANCE
SCA27B is an autosomal dominant inherited disorder. This means that individuals of any sex have the same likelihood of inheriting a single copy (allele) of the mutated gene and becoming carriers of the mutation. A child of a person with SCA27B has a 50% chance of inheriting a copy of the altered gene (assuming only one parent carries the mutation — either the biological mother or father).
Please note that in some cases, family history may not be evident (sporadic cases), either due to a new (de novo) mutation or because of incomplete penetrance (a parent had the mutation but did not exhibit significant symptoms).
As previously mentioned, the gene involved is FGF14 (fibroblast growth factor 14) — the mutation consists of an abnormal expansion of the GAA trinucleotide repeat in intron 1 of this gene, in a heterozygous state. Heterozygosity means that the second copy of the gene (inherited from the other parent) is usually normal. Conventional point mutations in FGF14 can also cause ataxia (in that case referred to as SCA27A), but this is a distinct condition with earlier onset, and it is classified separately from SCA27B. In SCA27B, the disease is specifically caused by repetitive GAA expansions.
GAA Repeat Range in the FGF14 Gene for Diagnosis:
The number of GAA repeats varies among individuals and determines whether the disease is present [3]:
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Normal range: 6 to 249 GAA repeats in FGF14 — this range does not cause ataxia.
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Intermediate range (reduced penetrance): 250 to 300 repeats — alleles in this range may or may not cause symptoms. There is incomplete penetrance: some individuals with this repeat size develop late-onset or mild ataxia, while others remain asymptomatic.
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Pathogenic range: over 300 GAA repeats — expansions above ~300 trinucleotides cause the disease and are found in nearly all symptomatic patients. This is the currently established diagnostic threshold for SCA27B (the “full mutation”).
As mentioned in section 4. Anticipation, these GAA expansions can change in size when passed from one generation to the next (from parents to children). It is important to note that only pure GAA expansions (uninterrupted, continuous repeats) are known to cause ataxia. If the repeat is interrupted by other sequences (i.e., not pure GAA), it does not appear to result in disease, even when long [3].
In very rare cases, an individual may inherit expansions in both copies of the gene (a situation known as homozygosity), i.e., inheriting one mutated allele from each parent. However, SCA27B is still considered a dominant disorder, since a single mutated copy (in the pathogenic range) is sufficient to cause ataxia symptoms.
Note: "Autosomal" means that the gene is located on a chromosome other than the sex chromosomes (X or Y). Genes, like chromosomes, typically come in pairs — one copy is inherited from the mother and the other from the father. "Dominant" means that a single copy of the altered gene (one allele), inherited from either parent, is enough to transmit a physical trait (such as cheek dimples) or a genetic disorder (like hereditary ataxias) from one generation (parents) to the next (children).
Figure 2 – Source: MedlinePlus, U.S. National Library of Medicine.
6. PREVALENCE
Since the gene whose mutation causes SCA27B was only identified in 2022, little is known about this type of ataxia, or its prevalence is not yet known [2]. There is still no robust estimate in terms of the number of cases per 100,000 population exclusively for SCA27B.
SCA27B is considered rare, but remarkably common compared to other inherited ataxias, especially in Western populations. Initial studies suggest it is among the most common genetic causes of adult-onset ataxia . SCA27B is believed to have a prevalence comparable to, or perhaps even greater than, SCA3, which is considered the most prevalent spinocerebellar ataxia (globally) .
Prevalence data vary by geographic region and population. Studies suggest that groups of European ancestry appear to be more likely to carry large FGF14 alleles that may expand into the pathogenic range [1] , while in Asian populations SCA27B appears to be much less common (in a survey of 312 Japanese patients with ataxia of unknown cause, no cases of SCA27B were identified). There are reports of particularly high prevalence in certain communities, such as French Canadians (French Canada), where the mutation has been found with notable frequency [2] .
7. ADDITIONAL INFORMATION
Diagnosis
The diagnosis of SCA27B can be confirmed through molecular genetic testing to detect a pathogenic GAA repeat expansion in the FGF14 gene, and is especially recommended if there is already a confirmed case in the family (positive family history of SCA27B).
Note! Detecting the SCA27B mutation requires specific repeat expansion tests. Common sequencing methods (such as multigene panels, whole exome, or short-read genome sequencing) generally do not detect this mutation, as it lies in an intronic region of the gene and involves a long repeat. Diagnosis is made using techniques like repeat-primed PCR (RP-PCR) or long-read sequencing, which can reveal large GAA expansions in the FGF14 gene [3].
Many ataxia cases that were previously considered “undiagnosed” (labeled idiopathic) have been clarified after the introduction of specific tests for SCA27B. It is now recommended that individuals with adult-onset cerebellar ataxia of unknown cause be screened for FGF14 expansions.
Relationship Between SCA27A and SCA27B
Before the discovery of the GAA expansion, it was already known that mutations in FGF14 could cause ataxia. Point mutations (such as missense or deletions) in FGF14 were described in 2005 and initially classified as SCA27 (now referred to as SCA27A). SCA27A presents a somewhat different phenotype — it tends to have an earlier onset (typically during adolescence or early adulthood), often beginning with tremor, followed later by ataxia. SCA27B, in contrast, is not caused by conventional mutations but by a repetitive intronic GAA expansion, with symptoms typically emerging later in life (middle age or older), often including downbeat nystagmus and episodic ataxia. Although both conditions involve the same gene (FGF14) and share a dominant inheritance pattern, they are genetically distinct — hence the “A” and “B” suffixes.
Imaging Findings
Neuroimaging can support the diagnosis of SCA27B. Brain MRI in many patients with SCA27B shows mild to moderate cerebellar atrophy, more prominent in the vermis (the central part of the cerebellum). However, atrophy is often mild in early stages and may even be absent in some cases at onset. With the disease’s slow progression, more generalized cerebellar atrophy may become apparent. Unlike some other dominant ataxias, brainstem involvement (such as pontine atrophy) is not typically expected, nor are lesions outside the cerebellum. Imaging helps to rule out other acquired differential diagnoses.
Differential Diagnosis with Episodic Ataxias
Because many individuals with SCA27B experience ataxia episodes at onset, there can be diagnostic confusion with primary episodic ataxias, such as EA2 (Episodic Ataxia Type 2), which is linked to the CACNA1A gene. However, EA2 usually begins in childhood or adolescence, while SCA27B onsets later in life [3]. In addition, SCA27B episodes may progress to a chronic, persistent ataxia over time, whereas in pure episodic ataxias, individuals may remain nearly asymptomatic between episodes for many years. The presence of downbeat nystagmus and a dominant family history also support a diagnosis of SCA27B.
It is now known that some cases previously diagnosed as “late-onset sporadic ataxia” or even as possible adult-onset EA were in fact SCA27B when tested genetically [1].
Importance of Diagnosis
Although it can be challenging, confirming a diagnosis of SCA27B has important implications. As one of the relatively more common late-onset genetic ataxias, several initiatives are underway to better understand its natural history and to develop treatments (see section 8: Therapies and Medications). Moreover, molecular diagnosis enables proper genetic counseling for families, helping distinguish SCA27B from other hereditary ataxias and allowing for risk assessment in offspring. Since penetrance may be incomplete in borderline cases, detecting the expansion in an asymptomatic individual (e.g., an elderly parent of a patient) does not necessarily mean they will develop ataxia, but it does indicate they could pass it on to their children. Therefore, predictive testing and genetic counseling should be offered under specialized guidance, given the particular nature of this repetitive mutation.
8. THERAPIES AND DRUGS BEING TRIALED FOR THIS ATAXIA
To date, there is no known cure for SCA27B, but several therapeutic approaches are being explored—both for symptomatic relief and in research aimed at disease-modifying treatments.
Medications
The drug 4-aminopyridine (4-AP), already available on the market for other neurological conditions, has shown promising results in managing symptoms of SCA27B. Initial studies and case reports suggest that 4-AP may reduce the frequency and severity of ataxia episodes, as well as improve ongoing coordination issues—particularly by helping to control downbeat nystagmus [3]. Approximately half of the patients experience reduced ocular oscillations and improved postural stability while using 4-AP. Therefore, this is a topic that should be discussed with a neurologist to assess the potential benefits and risks of trying this approach. It is worth noting that 4-AP must be used under neurological supervision, as side effects must be monitored (e.g., risk of seizures at high doses). See also [8] in section 10: References.
Gene-targeted therapies for GAA expansions
Since the SCA27B mutation is similar in nature to that of Friedreich's Ataxia (which also involves an intronic GAA expansion, though in a different gene and with recessive inheritance), there is growing interest in therapies that counteract the gene-silencing mechanism caused by such repeat expansions. One strategy under investigation involves small molecules that bind directly to the expanded GAA sequences in the DNA, preventing the formation of abnormal structures and restoring normal gene transcription [1]. As of now, no gene therapies for SCA27B have been published, but ongoing research is encouraging.
Ongoing clinical trials and research
Due to the relatively high prevalence of SCA27B and the availability of at least one potential symptomatic treatment (4-AP), the scientific community has made this condition a research priority. In 2023, an international consortium dedicated to SCA27B was launched, endorsed by the Ataxia Global Initiative (AGI), involving over 50 clinical centers worldwide. The goals include creating patient registries, standardizing biomarkers and clinical outcome measures, and laying the groundwork for future clinical trials. So far, this collaboration has identified more than 500 confirmed cases in 18 countries and is actively working to define the natural history of the disease [1]. Formal clinical trials are expected to begin in the near future.
Other symptomatic approaches
As with other ataxias, various supplements and medications are being tested to generally improve cerebellar function. Analogues of aminopyridine, such as 3,4-diaminopyridine, as well as drugs commonly used to treat tremor and vertigo, may be considered on a case-by-case basis. Some SCA27B patients with episodic symptoms have experimented with acetazolamide (a drug used in Episodic Ataxia Type 2), and while there are anecdotal reports of benefit, formal evidence is lacking. Interventions to manage spasticity or neuropathy (such as baclofen, gabapentin) may be prescribed depending on the symptoms (see section 9: Treatments).
Summary - Currently, treatment for SCA27B is primarily symptomatic and focused on rehabilitation, but there is strong scientific commitment toward developing targeted therapies. 4-aminopyridine stands out as a promising option to improve motor and ocular symptoms, while future therapies aimed at correcting the underlying genetic defect are under investigation. Patients with SCA27B (and other types of ataxia!) should be encouraged to participate in patient registries and clinical studies, when available, both to contribute to scientific progress and potentially gain access to promising experimental treatments.
9. TREATMENTS
SCA27B 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 patients are followed by a neurologist and a specialized multidisciplinary medical team, with the gradual inclusion of other healthcare professionals as needed depending on the symptoms (e.g., geneticist, neuro-ophthalmologist, neurofunctional physical therapist, occupational therapist, speech-language pathologist, nutritionist, etc.).
General recommendations for managing symptoms in SCA27B
Neurological Physiotherapy
Neurological physiotherapy is essential for helping patients with ataxia (whether SCA27B or another type) maintain mobility and balance for as long as possible. Coordination exercises, muscle strengthening, and gait training should be initiated early. The physiotherapist can guide the patient through safe, regular physical activities (including adapted home exercises). Fall prevention strategies should also be addressed [3].
Occupational Therapy
The occupational therapist supports the patient in optimizing activities of daily living (ADLs) by recommending techniques and tools to work around motor limitations. This may include adaptive utensils (e.g., weighted cutlery or pens for tremors), home adaptations (e.g., raised toilet seats, grab bars), and training in daily tasks to promote safety and independence. The goal is to preserve autonomy in personal care, work, and leisure for as long as possible.
Speech and Swallowing Therapy
Many individuals with SCA27B develop dysarthria (speech articulation difficulty). Speech therapy can improve vocal projection, speech clarity, and teach techniques to compensate for slow or slurred speech. In more severe cases, the speech therapist can introduce alternative communication methods (e.g., letter boards, apps, or voice-generating devices) [3].
If dysphagia (difficulty swallowing) is present, speech-language therapy also includes swallowing exercises and maneuvers to prevent choking or aspiration. Food texture adjustments and postural changes during meals may be recommended to ensure safe nutrition.
Ophthalmologic Care
Given the high prevalence of eye movement disorders in spinocerebellar ataxias, regular follow-up with an ophthalmologist or neuro-ophthalmologist is important. In some cases, 4-aminopyridine may significantly improve downbeat nystagmus and other oculomotor issues [3]. Prism lenses can help relieve diplopia (double vision) by aligning images to reduce overlap.
Environmental adaptations such as enhanced lighting (e.g., night lights for safe bathroom navigation) and limiting prolonged reading may help with oscillopsia. Managing visual symptoms can significantly improve balance and quality of life, as vision plays a key role in postural stability.
Tremor and Spasticity Management
If the patient experiences disabling tremors (e.g., arm tremor interfering with eating), medications used for essential or Parkinsonian tremors (such as propranolol, primidone, or others) may be considered. While spasticity (muscle stiffness) is not typically prominent in SCA27B, if painful or limiting spasticity occurs, stretching exercises are the preferred initial approach [3]. In rare cases of severe spasticity, baclofen or other muscle relaxants may be used cautiously, as they can cause sedation or weakness, increasing the risk of falls. Physiotherapy can also assist with spasticity through balanced strengthening and stretching techniques.
Autonomic Symptom Management
Some patients with spinocerebellar ataxia report urinary urgency or frequency. Evaluation by a urologist or neurologist can help rule out other causes and guide treatment (e.g., anticholinergics or beta-3 agonists for overactive bladder) [3]. Pelvic floor physiotherapy may also be helpful. Sexual dysfunction, such as erectile dysfunction, can be treated using standard therapies and specialized counseling. These symptoms may be under-recognized but can and should be managed. Orthostatic hypotension (drop in blood pressure when standing) is not typical of SCA27B, but if present, it should be treated to prevent instability (e.g., compression stockings, hydration, midodrine).
Nutritional Support
A balanced diet is recommended. If chewing or swallowing is difficult, involving a nutritionist in conjunction with a speech therapist is important. Avoiding obesity is advisable, as excess weight places further strain on gait and balance. Conversely, excessive weight loss due to dysphagia or other causes should be prevented with appropriate nutritional supplementation.
While there is no solid evidence supporting antioxidant vitamins or supplements in SCA27B, maintaining adequate levels of vitamin D, B12, and other nutrients under medical guidance is considered good practice in ataxia care.
Psychosocial Support
Living with progressive ataxia (of any type) can have emotional consequences. Anxiety, depression, and social isolation are not uncommon. Psychological counseling or therapy may help patients cope with limitations and maintain motivation for treatment. Support groups and patient associations can provide a sense of community and shared experience. Social workers may assist families in accessing resources, home modifications, and rehabilitation services. Patient and caregiver education is essential, as is encouraging a proactive attitude toward treatment. If needed, medications for anxiety or depression can be prescribed under medical guidance.
Additional Recommendations
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Avoid alcohol and extreme physical exertion, as they may trigger or worsen ataxia episodes.
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As symptoms progress, assistive devices (e.g., canes, walking sticks, walkers) may be needed to increase stability.
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Simple home adaptations—grab bars in bathrooms, removal of loose rugs, appropriate footwear—can help prevent accidents.
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Rest as needed, and prioritize good-quality nighttime sleep. Consult a physician if sleep issues arise; CBD oil may be considered.
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Maintain healthy eating and adequate hydration.
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Minimize stress as much as possible, as it can exacerbate symptoms.
Note: Some patients with various types of cerebellar ataxia report improvement in symptoms following neuromodulation or non-invasive cerebellar stimulation, such as transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) performed by certified physiotherapists. However, while these therapies are commercially available, they have not been approved by the FDA in the U.S. (or ANVISA in Brazil) for the treatment of ataxia—meaning these are experimental treatments 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:
David Pellerin et al
© Copyright PubMed Central
Language:
English
Date:
2024 Jan 27
Ref #2
Source:
SCA27B sheet
© National Ataxia Foundation
Language:
English
Date:
2024
Ref #3
Source:
David Pellerinet al
© Copyright GeneReviews
Language:
English
Date:
January 25, 2024
Ref #4
Source:
Fernanda Laezza et al
© Copyright PubMed Central
Language:
English
Date:
2009
Ref #5
Source:
OMIM® - An Online Catalog of Human Genes and Genetic Disorders.
Copyright © Johns Hopkins University.
Language:
English
Date:
Edit History: carol: 02/04/2021
Ref #6
Source:
Presented by: Dr. Bernard Brais and Dr. David Pellerin
YouTube - Copyright © National Ataxia Foundation (NAF)
Language:
English. You can enable subtitles and configure automatic translation of subtitles into Portuguese.
Date:
Nov 15, 2023
Ref #7
Source:
Presented by: Dr. Bernard Brais and Dr. David Pellerin
YouTube - Copyright © National Ataxia Foundation (NAF)
Language:
English. You can enable subtitles and configure automatic translation of subtitles into Portuguese.
Date:
Dec 20, 2023
Ref #8
Source:
Carlo Wilke et al
PubMed - Brain. 2023 Oct 3;146(10):4144-4157. doi: 10.1093/brain/awad157. PMID: 37165652.
Language:
English.
Date:
2023