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Spinocerebellar ataxia type 7: clinical course, phenotype-genotype correlations, and neuropathology
- Source :
- Cerebellum (London, England). 12(2)
- Publication Year :
- 2012
-
Abstract
- Spinocerebellar ataxia type 7 is a neurodegenerative polyglutamine disease characterized by ataxia and retinal degeneration. The longitudinal course is unknown, and relationships between repeat expansion, clinical manifestations, and neuropathology remain uncertain. We followed 16 affected individuals of a 61-member kindred over 27 years with electroretinograms, neurological examinations including the Brief Ataxia Rating Scale, neuroimaging in five, and autopsy in four cases. We identified four stages of the illness: Stage 0, gene-positive but phenotypically silent; Stage 1, no symptoms, but hyperreflexia and/or abnormal electroretinograms; Stage 2, symptoms and signs progress modestly; and Stage 3, rapid clinical progression. CAG repeat length correlated inversely with age of onset of visual or motor signs (r = −0.74, p = 0.002). Stage 3 rate of progression did not differ between cases (p = 0.18). Electroretinograms correlated with Brief Ataxia Rating Scale score and were a biomarker of disease onset and progression. All symptomatic patients developed gait ataxia, extremity dysmetria, dysarthria, dysrhythmia, and oculomotor abnormalities. Funduscopy revealed pale optic discs and pigmentary disturbances. Visual acuity declined to blindness in those with longer CAG expansions. Hyperreflexia was present from Stage 1 onwards. Restless legs syndrome and sensory impairment were common. Neuropathological hallmarks were neuronal loss in cerebellar cortex, deep cerebellar nuclei, inferior olive, and anterior horns of the spinal cord, and axonal loss in spinocerebellar tracts, dorsal nerve roots, and posterior columns. Retinal pathology included photoreceptor degeneration and disruption of retinal pigment epithelium. Spinocerebellar ataxia type 7 evolves through four clinical stages; neuropathological findings underlie the clinical presentation; electroretinograms are a potential biomarker of disease progression.
- Subjects :
- Adult
Male
congenital, hereditary, and neonatal diseases and abnormalities
Pathology
medicine.medical_specialty
Ataxia
genetic structures
Intranuclear Inclusion Bodies
Nerve Tissue Proteins
Neuropathology
Hyperreflexia
Severity of Illness Index
Article
Young Adult
Trinucleotide Repeats
Dysmetria
Diagnosis
medicine
Electroretinography
Humans
Spinocerebellar Ataxias
Longitudinal Studies
Genetic Association Studies
Aged
Retrospective Studies
Aged, 80 and over
Ataxin-7
Family Health
Neurons
Spinocerebellar tract
Age Factors
Brain
Middle Aged
medicine.disease
Magnetic Resonance Imaging
medicine.anatomical_structure
Neurology
Cerebellar cortex
Spinocerebellar ataxia
Gait Ataxia
Female
Neurology (clinical)
medicine.symptom
Psychology
Photic Stimulation
Subjects
Details
- ISSN :
- 14734230
- Volume :
- 12
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cerebellum (London, England)
- Accession number :
- edsair.doi.dedup.....f22744ae65f7c50e9167953218a6a074