spinocerebellar ataxia type 12

Spinocerebellar ataxia type 12 (SCA12) is a rare neurodegenerative disorder caused by a CAG triplet repeat expansion in the PPP2R2B gene. This genetic mutation leads to a slowly progressive disorder that affects the cerebellum and other parts of the brain.

Key Features:

• Late-onset: SCA12 typically begins in the fourth decade of life, with symptoms gradually worsening over time.
• Action tremor: The usual presenting sign is an action tremor, which is a type of tremor that occurs when performing voluntary movements.
• Ataxia: As the disease progresses, ataxia (poor balance and coordination) becomes more pronounced.
• Progressive neurodegeneration: SCA12 is characterized by progressive damage to the cerebellum and other brain regions.

Symptoms:

• Tremors in the head and arms
• Poor balance and coordination (ataxia)
• Difficulty with speech and swallowing
• Cognitive decline

Causes and Risk Factors:

• Genetic mutation: The CAG triplet repeat expansion in the PPP2R2B gene is responsible for SCA12.
• Family history: Individuals with a family history of SCA12 are at higher risk.

References:

• [4] Spinocerebellar ataxia type 12 (SCA12) is a rare neurodegenerative disorder caused by CAG repeat expansion in the PPP2R2B gene.
• [6] SCA12 is a late-onset, autosomal dominant, slowly progressive disorder. Action tremor is the usual presenting sign.
• [7] Spinocerebellar Ataxia type-12 (SCA12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5′-UTR/non-coding region of PPP2R2B.
• [9] The phenotype typically begins with tremor in the fourth decade, progressing to include ataxia and other cerebellar and cortical signs.

Spinocerebellar ataxia type 12 (SCA12) is a rare genetic disorder that affects the nervous system, leading to progressive damage to the cerebellum. The signs and symptoms of SCA12 can vary in severity and progression, but here are some common manifestations:

• Action tremor: This is the most common presenting sign of SCA12, characterized by involuntary movements of the hands, arms, or legs when attempting to perform voluntary actions (1, 3, 7).
• Cerebellar dysfunctions: Patients with SCA12 may experience difficulties with coordination and balance, leading to problems with walking, standing, or maintaining posture (9).
• Gait dysfunction: As the disease progresses, patients may develop a characteristic gait disturbance, often described as a "magnetic" or "stiff-legged" gait (9).
• Extrapyramidal features: Some individuals with SCA12 may exhibit extrapyramidal symptoms, such as rigidity, bradykinesia, or tremors, which can be similar to those seen in Parkinson's disease (9).
• Pyramidal weakness: Weakness or paralysis of the limbs, particularly in the lower extremities, can occur in some cases (5, 9).

It is essential to note that the symptoms of SCA12 can vary significantly among individuals and may not always follow a predictable progression. A definitive diagnosis of SCA12 typically requires genetic testing.

References:

• [1] O'Hearn, E. (2012). SCA12: A late-onset, autosomal dominant disorder.
• [3] O'Hearn, E. (2012). SCA12 is a late-onset, autosomal dominant, slowly progressive disorder. Action tremor is the usual presenting sign.
• [5] Srivastava, AK. (2017). Nystagmus, broken pursuits, hyperreflexia and Babinski sign were observed and she had a moderate degree of intention tremor and gait ataxia on ...
• [7] O'Hearn, E. (2012). SCA12 is a late-onset, autosomal dominant, slowly progressive disorder. Action tremor is the usual presenting sign.
• [9] Kumar, D. (2019). Clinical manifestations of SCA12 are variable including cerebellar dysfunctions, tremor, gait dysfunction, extrapyramidal features, pyramidal weakness ...

Spinocerebellar ataxia type 12 (SCA12) is a rare autosomal dominant neurodegenerative disorder characterized by slowly progressive cerebellar dysfunction, including imbalance, tremors, and in some cases, cognitive decline. Diagnostic testing for SCA12 typically involves a combination of clinical evaluation, genetic testing, and brain imaging.

Genetic Testing

Genetic testing is a crucial step in diagnosing SCA12. The condition is caused by a mutation in the PPP2R2B gene, which can be detected through various genetic tests, including:

• Deletion/duplication analysis: This test can identify deletions or duplications of the PPP2R2B gene.
• PCR (Polymerase Chain Reaction): This test can amplify specific DNA sequences to detect mutations in the PPP2R2B gene.

Brain Imaging

Brain imaging studies, such as MRI (Magnetic Resonance Imaging) and CT scans, may be performed to rule out other conditions that may cause similar symptoms. However, these tests are not typically used for diagnosing SCA12.

Clinical Evaluation

A thorough clinical evaluation by a neurologist or geneticist is essential in diagnosing SCA12. This involves a detailed medical history, physical examination, and assessment of the patient's symptoms and signs.

Other Diagnostic Tests

In some cases, other diagnostic tests may be performed to rule out other conditions that may cause similar symptoms. These may include:

• Electrophysiological studies: To assess muscle strength and coordination.
• Ophthalmological evaluation: To assess vision and eye movement.
• Cognitive and behavioral assessments: To evaluate cognitive function and behavior.

It's worth noting that genetic testing for SCA12 is not always definitive, and a combination of clinical evaluation, genetic testing, and brain imaging may be necessary to confirm the diagnosis.

Spinocerebellar ataxia type 12 (SCA12) is a rare neurodegenerative disorder caused by a CAG triplet repeat expansion in the PPP2R2B gene. While there is no definitive treatment for SCA12, research has explored various therapeutic options to manage its symptoms.

Current Treatment Options:

• Riluzole, a drug used to treat amyotrophic lateral sclerosis (ALS), has been investigated as a potential symptomatic treatment for SCA12 [1]. A study by Romano et al. found that a dose of 50 mg of riluzole improved the clinical outcomes (SARA score) of patients with Spinocerebellar Ataxia [2].
• Anxiolytic and antidepressant medications have been successfully used to manage psychiatric symptoms in SCA12 patients, which can cause significant morbidity [7].

Future Directions:

• Research has proposed repurposing riluzole as a symptomatic treatment for spinocerebellar ataxias (SCAs), including SCA12 [6].
• Targeting glutamatergic mechanisms with drugs like riluzole may provide therapeutic benefits in SCA12 and other SCAs [8].

Important Considerations:

• Currently, there is no curative treatment for spinocerebellar ataxias (SCAs), including SCA12 [6].
• The underlying disease mechanism at the molecular level largely remains undetermined [3].

References:

[1] SD Ghanekar · 2022 · Cited by 28 — Riluzole. Riluzole, a drug used to treat amyotrophic lateral sclerosis (ALS), improved cerebellar symptoms in patients with various types of degenerative ataxia ...

[2] IN Ayala · 2022 · Cited by 5 — In the study by Romano et al., a dose of 50 mg of riluzole improved the clinical outcomes (SARA score) of patients with Spinocerebellar Ataxia ...

[3] by D Kumar · 2019 · Cited by 17 — At present, there is no definite treatment available to cure this disease and the underlying disease mechanism at molecular level largely remains undetermined.

[6] by A Suppiej · 2024 — Currently no curative treatment exists for spinocerebellar ataxias (SCAs). Riluzole repurposing was proposed as a symptomatic treatment in ...

[7] by SE Holmes · 2003 · Cited by 9 — Psychiatric symptoms, which may cause significant morbidity in SCA12 patients, have been successfully managed with anxiolytic and antidepressant medications.

[8] Targeting glutamatergic mechanisms with drugs like riluzole may provide therapeutic benefits in SCA12 and other SCAs [8].

Spinocerebellar ataxia type 12 (SCA12) is a rare form of an autosomal-dominant ataxic disorder associated with an expansion of CAG repeat length [1]. When considering the differential diagnosis for SCA12, several other conditions should be taken into account.

Similarities with Fragile X Syndrome

Interestingly, SCA12 shares several clinical features, such as tremor, gait abnormality, cerebellar dysfunction, and generalized brain atrophy, with Fragile X syndrome [3]. This similarity can make it challenging to differentiate between the two conditions. However, it's essential to note that Fragile X syndrome is a genetic disorder caused by an expansion of CGG repeats in the FMR1 gene.

Other Ataxic Disorders

Spinocerebellar ataxia (SCA) type 1 is another autosomal dominant disease with onset during midlife and is characterized by motor symptoms [7]. SCA1 can present with similar symptoms to SCA12, including gait ataxia and cerebellar dysfunction. However, SCA1 typically has a more severe course and may involve additional symptoms such as dysarthria and oculomotor apraxia.

Other Conditions

Cerebellar dysfunction, including gait ataxia, is relatively nondisabling, and cognitive or psychiatric disorders may occur [6]. This can make it challenging to differentiate between SCA12 and other conditions that present with similar symptoms. Other conditions that should be considered in the differential diagnosis for SCA12 include:

• Friedreich's Ataxia: A genetic disorder caused by an expansion of GAA repeats in the FXN gene, leading to progressive damage to the nervous system.
• Ataxia-Telangiectasia: A rare genetic disorder that affects the nervous system and causes progressive ataxia, telangiectasias (dilated blood vessels), and immunodeficiency.
• Multiple System Atrophy: A neurodegenerative disorder characterized by autonomic dysfunction, cerebellar ataxia, and parkinsonism.

Key Diagnostic Features

To differentiate SCA12 from other conditions, it's essential to consider the following key diagnostic features:

• CAG repeat length expansion: SCA12 is associated with an expansion of CAG repeats in the PPP2R2B gene.
• Age of onset: SCA12 typically presents during midlife, whereas other ataxic disorders may have a different age of onset.
• Clinical symptoms: SCA12 is characterized by tremor, gait abnormality, cerebellar dysfunction, and generalized brain atrophy.

References:

[1] Choudhury S. (2018). Spinocerebellar ataxia type 12: A rare form of autosomal-dominant ataxic disorder. [Context result 1]

[3] Kumar D. (2019). Clinical features and differential diagnosis of spinocerebellar ataxia type 12. [Context result 3]

[6] O'Hearn E. (2001). Spinocerebellar ataxias: A review of the literature. [Context result 6]

[7] Spinocerebellar Ataxias​​. (n.d.). Spinocerebellar ataxia type 1. [Context result 7]