Natural History of Spinocerebellar Ataxia Type 7 (SCA7)

Overview

Background: Spinocerebellar ataxia type 7 (SCA7) is a disease in which people have problems with coordination, balance, speech and vision. It is caused by a change in the ATXN7 gene. A mutation in this ATXN7 gene causes changes in eye cells, which can lead to vision loss. There is no cure for SCA7 but researchers are looking for possible treatments. Researchers need more information about SCA7. They want to collect vision and neurology related data from people with SCA7. They want to learn how and what changes in the eye and brain when the ATXN7 gene isn t working properly. Objective: To learn more about SCA7 and its progression. Eligibility: People ages 12 and older with SCA7. Design: Participants will be screened with medical history and genetic testing from a previous National Eye Institute study or their personal physician. Participants will have at least 7 visits over 5 years. They will have 2 visits during the first week of the study. Then they will be asked to come back every year for the next 5 years. Each visit will last several days and will include: * Medical and eye history * Several eye tests: some will include dilating the pupil with eye drops and taking photos or scans of the eyes. * Electroretinography (ERG): Participants will sit in the dark with their eyes patched for 30 minutes. After this, the patches will be removed and contact lenses put into the eyes. They will watch flashing lights and information will be recorded. * Neurological exams: Sensation, strength, coordination, reflexes, attention, memory, language, and other cognitive functions will be tested. * Brain MRI: They will lie in a machine that takes pictures of the brain. * Blood and urine tests * Optional skin biopsy: About 3 millimeters of skin will be removed for more research testing; this is half the size of a pencil eraser.

Objective: Spinocerebellar Ataxia, type 7 (SCA7) is an autosomal dominant neurodegenerative disease characterized by progressive ataxia, retinal degeneration, and marked genetic anticipation. The objectives of this study are to 1) establish a cohort of participants with molecularly-confirmed SCA7 in anticipation of future clinical trials, 2) create a repository of plasma, DNA, and skin fibroblast samples from the accrued cohort of SCA7 participants, 3) formulate clinical outcome measures for future studies, and 4) acquire and perform preliminary analyses of data that may advance our understanding of the progression of retinal and neurodegeneration associated with molecularly-confirmed SCA7. Study Population: Twenty-five (25) participants, ages 12 and above, with molecularly-confirmed SCA7 will be accrued for this study. Design: In this natural history study, participants will be followed for at least five years. Because three years may be required to enroll 25 participants, this study will last at least eight years. All participants will undergo a standardized medical/ophthalmic history and a complete baseline eye examination, including non-invasive electrophysiology (e.g., electroretinography), psychophysiology (e.g., microperimetry, static perimetry), and diagnostic imaging examinations (e.g., optical coherence tomography). In addition, participants will undergo a detailed neurology exam, neuroimaging (MRI, including special sequences) and consult with speech pathology and/or other rehabilitation services, audiology, and neuropsychology. To establish baseline, the participants will undergo two separate detailed eye examinations and a single neurology/neuroimaging examination within a one to two week period. Afterwards, they will return to the NEI clinic annually until the last-enrolled participant has completed a minimum of five study visits. Follow-up visits will consist of a single detailed eye exam, a single detailed neurology/neuroimaging exam, and follow-up with appropriate consultants. Participants may be seen at more frequent intervals at the investigators discretion, depending on the clinical and research situation. Participants will be required to submit a blood sample for research, and they will have the option to provide a skin biopsy to facilitate research at a cellular level. Outcome Measures: The primary outcome for this study is determination of the amplitude and time of photopic and scotopic responses on electroretinogram. Secondary outcomes include changes in visual acuity, microperimetry, peripheral visual field, color vision, macular thickness, and neurologic outcome variables. Exploratory outcomes for this study include: 1) the formulation of clinical outcome measures for future studies and 2) the acquisition and preliminary analysis of data that may advance our understanding of the progression of retinal and neurodegeneration associated with molecularly-confirmed SCA7. Cells from skin biopsies may be grown in the laboratory to better understand SCA7, including the evaluation of potential treatments.