To characterize the clinical phenotype regarding retinal function and macular appearance in patients with spinocerebellar ataxia type 7 (SCA 7), with an emphasis on electrophysiological findings.
Three patients from two Swedish families were given an ophthalmological examination including visual acuity, fundus inspection, Farnsworth's color vision test, Goldmann perimetry, full-field electroretinography (full-field ERG), multifocal electroretinography (mfERG) and optical coherence tomography (OCT). DNA was analyzed with polymerase chain reaction for CAG trinucleotide expansion repeats in the SCA 7 gene.
Molecular analysis demonstrated abnormally expanded CAG repeats in the gene for SCA 7, which encodes the protein ataxin-7, thus confirming the diagnosis SCA 7. In the oldest patient very discreet pigmentary changes in the maculae were found, but with that exception the patients had a normal ophthalmoscopic fundus appearance and OCT demonstrated only minor changes. MfERG indicated predominantly central involvement, especially in the early disease stages, which in pace with disease progression extended from the center to the more peripheral areas. Full-field ERG in the oldest patient demonstrated bilaterally distinctly prolonged 30-Hz flicker implicit time, verifying widespread cone photoreceptor degeneration.
The patients with genetically confirmed SCA 7 presented an early macular dysfunction, preceding any signs of abnormalities in fundus appearance. According to the electrophysiological findings the primary dysfunction involves the cone photoreceptors in the foveal region, however in an older patient involvement of cone photoreceptors throughout the retina was verified. This is in accordance with the theory that ataxin-7 interacts with CRX transcription, since it is known that mutations in the CRX gene cause cone-rod dystrophy.
[Show abstract][Hide abstract] ABSTRACT: Two patients with genetically confirmed spinocerebellar ataxia type 7 (SCA7) presented with progressive visual loss. Examination disclosed substantial visual acuity loss, central scotomas, and marked dyschromatopsia. Ophthalmoscopic abnormalities were subtle, with only mild retinal artery attenuation and minimal foveal region pigmentary abnormalities. Both patients had slow saccades and partially limited ductions, although neither reported diplopia. One patient had obvious extremity and gait ataxia, but the other had only an unsteady tandem gait. Results of electroretinography (ERG) were abnormal in both patients. These cases illustrate that SCA7 may present with profound visual loss yet minimal ophthalmoscopic findings and sometimes minimal ataxia. The clues to diagnosis are the abnormal color vision, retinal artery attenuation, abnormal eye movements, and a family history of similar manifestations, which may have gone undiagnosed. Full-field or multifocal ERG will always disclose photoreceptor dysfunction. Genetic testing is now available to confirm the diagnosis.
Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society 10/2009; 29(3):187-91. DOI:10.1097/WNO.0b013e3181b41764 · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Spinocerebellar ataxia type 7 (SCA7) is a progressive ataxia that is unique among inherited ataxias in having a high prevalence of retinal photoreceptor abnormalities. However, the ophthalmic features and their relationship to the neurologic features of SCA7 have not been widely reported. The goal of this study was to provide increased documentation.
The medical records of 10 consecutive patients with SCA7 examined in the Neuro-Ophthalmology Clinic at Kresge Eye Institute between 2000 and 2008 were reviewed retrospectively. Each patient underwent a standardized ophthalmologic and neurologic examination. Some patients also underwent electroretinography (ERG). Eight patients had genetically confirmed disease and 2 patients had presumptive SCA7 based on their clinical presentation. Patients were excluded if they had visual loss or ataxia due to other causes.
Nine patients reported visual symptoms at presentation, including hemeralopia, photophobia, dyschromatopsia, and blurred vision. In 3 of these patients, the visual symptoms had preceded the onset of ataxic symptoms. Visual acuity was abnormal in all patients at presentation. Four patients with visual dysfunction had normal or minimally abnormal macular pigmentary changes, but all patients had abnormal electroretinograms (ERGs) showing primarily cone dysfunction. The severity of visual loss and the severity of ataxia were frequently discordant.
Based on this study, patients with SCA7 often have visual symptoms that may precede, accompany, or follow the onset of ataxic symptoms. The severity of vision loss and ataxia may be discordant. Ophthalmoscopic evidence of macular abnormalities may be scant, but results of ERG will always be abnormal. This information may assist in earlier and more cost-effective diagnosis and permit more effective patient counseling.
Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society 10/2009; 29(3):180-6. DOI:10.1097/WNO.0b013e3181b1b3f8 · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The spinocerebellar ataxias (SCAs) are a phenotypically and genetically diverse group of autosomal dominant disorders that cause pathological degeneration in the cerebellum, brainstem, and retina, resulting in a wide variety of ophthalmologic signs and symptoms.
The genetic discrimination of the SCAs has advanced dramatically over the past decade. The most common genetic (mutational) mechanism for the SCAs is an abnormal expansion to a stretch of glutamine amino acid residues (polyglutamine tract) encoded by any of several SCA-causing genes. Knowledge regarding the pathophysiology of polyglutamine-expansion-induced protein dysfunction is an area of intense investigation.
The ophthalmologist may be the first to encounter a patient with SCA, and a review of the most common genetic subtypes of this disorder is helpful in diagnosis and management.
Current opinion in ophthalmology 11/2010; 21(6):447-53. DOI:10.1097/ICU.0b013e32833eaf71 · 2.50 Impact Factor
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