Macular Dysfunction and Morphology in Spinocerebellar Ataxia Type 7 (SCA 7)

Department of Ophthalmology, Central Hospital, Kristianstad, Sweden.
Ophthalmic Genetics (Impact Factor: 1.46). 04/2009; 30(1):1-6. DOI: 10.1080/13816810802454081
Source: PubMed


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.

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    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.
    No preview · Article · Oct 2009 · Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society
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    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.
    Full-text · Article · Oct 2009 · Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society
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    ABSTRACT: Spinocerebellar ataxia type 7 (SCA7) is known as an autosomal dominant cerebellar ataxia; patients with genetically confirmed diagnoses of SCA7 have increased rapidly in recent years. However, SCA7 is a rare subtype of SCA, and most data available about SCA7 are those of white people. The aim of the present study was to systematically review the prevalence and clinical and genetic aspects of SCA7 patients in East Asian population. A search for publications on SCA7 was performed by using the "PubMed" database with the published language limited in English. Publications mainly focusing on the prevalence of SCA7 in patients with SCA and the clinical and genetic features of SCA7 patients were fully reviewed and analyzed. The prevalence of SCA7 in SCA patients ranged from 0 to 7.7%, which was similar to those reported previously. The clinical manifestations were typically present at the 30's of its victims (median, 29 years; interquartile range (IQR), 19.5-36.5 years), and the symptoms appeared 15 years ((15.17+/-4.22) years) earlier on average in the offspring than in the parents. Gait ataxia and visual impairment were both found in all patients of whom the clinical features were described. Mutant SCA7 alleles contained 40-100 CAG repeats, with a median of 47 repeats (IQR, 44.5-50.0); and the offspring had 13 more repeats on average compared with their parents (12.62+/-19.03). A strong negative correlation was found between CAG repeat size and the onset age of patients (r=-0.739, P=0.000). In addition, no significant difference was found in CAG repeat sizes between patients with visual impairment as the initial symptom and those with gait disturbance as their initial symptom (P=0.476). The prevalence of SCA7 in SCA patients, the age at onset and CAG repeats of SCA7 patients in East Asia are consistent with those of white people. However, larger population study is needed to assess the correlation between the CAG repeat size and initial symptoms of SCA7 patients in East Asia.
    No preview · Article · Aug 2010 · Chinese medical journal
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