Clinical characterisation and the improved molecular diagnosis of autosomal dominant cone-rod dystrophy in patients with SCA7

Abstract

Purpose To evaluate the retinal phenotype and genetic features of Chinese patients with spinocerebellar ataxia type 7 (SCA7). Methods Detailed ophthalmic examinations, including electroretinograms, fundus photography, fundus autofluorescence and optical coherence tomography, were performed to analyse the retinal lesions of patients with SCA7. A molecular genetic analysis was completed to confirm the number of CAG repeats in ATXN7 gene on the patients and their family members. Results Eight patients from three families with SCA7 were included in this study. Trinucleotide repeat was expanded from 43 to 113 in the affected patients. The affected patients were characterised by different degrees of cone-rod dystrophy, which is positively related to the number of CAG repeats and age. All patients complained of progressive bilateral visual loss, and most cases reported visual disturbance earlier than gait movement or dysarthria. A coarse granular appearance of the macular region on scanning laser ophthalmoscopy, hypofluorescence in the macula on autofluorescence, retinal atrophy on optic coherence tomography, depression of multifocal electroretinograms and prominent abnormalities in cone-mediated responses on electrograms are the general features of SCA7-related retinopathy. Hyperreflective dots in the outer retinal layers and choroidal vessel layers are a common sign in optic coherence tomography in the advanced stage. Conclusions SCA shows a cone-rod dystrophy phenotype. The multimodal imaging of the retina is beneficial to detect the early lesions of cone-rod dystrophy related to SCA7.

Multimodal Ophthalmic Imaging in Spinocerebellar Ataxia Type 7

“…Abe et al also utilized 633-nm SLO imaging and demonstrated a granular aspect of the posterior pole in five of the six patients they examined [14]. Loss of the ellipsoid layer, RPE changes, and decreased central retinal thickness have been reported numerous times [13,15,17,18,21,28,31,32], indicating how the central cones become affected at an early stage of the disease. In a case series including seven patients, Manrique et al investigated the RNFL peripapillary thickness and revealed reduced thickness in all their patients, with common sparing of the temporal peripapillary quadrant.…”

“…Katagiri et al recorded preserved rod responses in one patient [18]; Miller et al performed full-field ERG on four patients who had affected cone responses, while only one patient showed a combination of cone and rod degeneration [19]. On other occasions, the scotopic response decreased to some degree or as much as the photopic response, suggestive of cone-rod dystrophy [11,19,22,25,27,30,31]. Multifocal ERG (mfERG), evaluating the cone function in localized areas of the macular region, recorded significantly reduced amplitudes within the foveal area; in more advanced patients, amplitudes were reduced even in the outer mfERG areas [17].…”