The Pathophysiology and Clinical Manifestations of Spinocerebellar Ataxia Type 6

Rentiya, Zubir; Hutnik, Robert; Mekkam, Yolunna Q; Bae, Junun

doi:10.1007/s12311-020-01120-y

Cited by 16 publications

(6 citation statements)

References 27 publications

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“…Dysarthria and episodic vertigo can also be early symptoms preceding gait disturbance (9). In addition, clinical signs, including hyperreflexia, basal ganglia signs and parkinsonism signs, are relatively common in SCA6 (45,88). Cognitive dysfunction, such as impairment in the retrieval of memorized information (89), visual memory and verbal fluency (90), can also be present.…”

Section: Sca Typementioning

confidence: 99%

Visual oculomotor abnormalities and vestibulo‑ocular reflex dynamics in polyglutamine spinocerebellar ataxias (Review)

Peng

Han

et al. 2023

Exp Ther Med

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Spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases that are characterized by cerebellar ataxia. The most common types of SCAs are caused by polyglutamine (polyQ)-encoding cytosine-adenine-guanine repeat expansions. Autosomal dominant SCAs share similar pathophysiological mechanisms. The cerebellum plays an important role in the generation and control of eye movement, and neuropathological findings indicate that cerebellar degeneration is commonly present in polyQ-SCAs. As a result, various patterns of oculomotor impairment are present in most SCA subtypes. The present review summarizes the visual oculomotor abnormalities and vestibulo-ocular reflex dynamics of the most common polyQ-SCAs, as well as their genetic, clinical and neuropathological features. In conclusion, the systemic evaluation of eye movement features is useful in the differential diagnosis of polyQ-SCAs. Contents1. Introduction 2. SCA type 1 3. SCA type 2 4. SCA type 3 5. SCA type 6 6. SCA type 7 7. SCA type 17 8. Conclusions

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Section: Sca Typementioning

confidence: 99%

Visual oculomotor abnormalities and vestibulo‑ocular reflex dynamics in polyglutamine spinocerebellar ataxias (Review)

Peng

Han

et al. 2023

Exp Ther Med

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“…Recent studies have found that α1ACT is involved in the regulation of genes associated with the function of Purkinje cell development [ 24 ]. In an autopsy study in early-onset SCA6, Purkinje cells were found to have reduced dendritic mass and spines, as well as reduced dendritic branching complexity [ 25 , 26 ]. Recent studies have shown that patients with CACNA1A mutations exhibit atrophy of the cerebellum during development, which is a recognizable neurodevelopmental disorder [ 27 ].…”

Section: Increasing Evidence Linking Purkinje Cell Dendritic Developm...mentioning

confidence: 99%

The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint

Kapfhammer

2022

IJMS

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Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominantly inherited progressive disorders with degeneration and dysfunction of the cerebellum. Although different subtypes of SCAs are classified according to the disease-associated causative genes, the clinical syndrome of the ataxia is shared, pointing towards a possible convergent pathogenic pathway among SCAs. In this review, we summarize the role of SCA-associated gene function during cerebellar Purkinje cell development and discuss the relationship between SCA pathogenesis and neurodevelopment. We will summarize recent studies on molecules involved in SCA pathogenesis and will focus on the mGluR1-PKCγ signaling pathway evaluating the possibility that this might be a common pathway which contributes to these diseases.

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“…SCA6 is distinguished from the other common SCAs in that it exhibits a pure cerebellar cortical syndrome without brainstem involvement and extracerebellar clinical manifestations (Rentiya et al, 2020). Only SCA6 among autosomal dominant SCAs belongs to ADCA type 3.…”

Section: Spinocerebellar Ataxia Typementioning

confidence: 99%

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

2020

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Spinocerebellar ataxia (SCA) is a part of the cerebellar neurodegenerative disease group that is diverse in genetics and phenotypes. It usually shows autosomal dominant inheritance. SCAs, always together with the cerebellar degeneration, may exhibit clinical deficits in brainstem or eye, especially retina or optic nerve. Interestingly, autosomal dominant SCAs share a common genetic mechanism; the length of the glutamine chain is abnormally expanded due to the increase in the cytosine-adenine-guanine (CAG) repeats of the disease causing gene. Studies have suggested that the mutant ataxin induces alteration of protein conformation and abnormal aggregation resulting in nuclear inclusions, and causes cellular loss of photoreceptors through a toxic effect. As a result, these pathologic changes induce a downregulation of genes involved in the phototransduction, development, and differentiation of photoreceptors such as CRX, one of the photoreceptor transcription factors. However, the exact mechanism of neuronal degeneration by mutant ataxin restricted to only certain type of neuronal cell including cerebellar Purkinje neurons and photoreceptor is still unclear. The most common SCAs are types 1, 2, 3, 6, 7, and 17 which contain about 80% of autosomal dominant SCA cases. Various aspects of eye movement abnormalities are evident depending on the degree of cerebellar and brainstem degeneration in SCAs. In addition, certain types of SCAs such as SCA7 are characterized by both cerebellar ataxia and visual loss mainly due to retinal degeneration. The severity of the retinopathy can vary from occult macular photoreceptor disruption to extensive retinal atrophy and is correlated with the number of CAG repeats. The value of using optical coherence tomography in conjunction with electrodiagnostic and genetic testing is emphasized as the combination of these tests can provide critical information regarding the etiology, morphological evaluation, and functional significances. Therefore, ophthalmologists need to recognize and differentiate SCAs in order to properly diagnose and evaluate the disease. In this review, we have described and discussed SCAs showing ophthalmic abnormalities with particular attention to their ophthalmic features, neurodegenerative mechanisms, genetics, and future perspectives.

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The Pathophysiology and Clinical Manifestations of Spinocerebellar Ataxia Type 6

Cited by 16 publications

References 27 publications

Visual oculomotor abnormalities and vestibulo‑ocular reflex dynamics in polyglutamine spinocerebellar ataxias (Review)

Visual oculomotor abnormalities and vestibulo‑ocular reflex dynamics in polyglutamine spinocerebellar ataxias (Review)

The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

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