1. CDH23-Associated Usher Syndrome: Clinical Features, Retinal Imaging, and Natural History.
- Author
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de Guimaraes TAC, Robson AG, de Guimaraes IMC, Laich Y, Aychoua N, Wright G, Kalitzeos A, Mahroo OA, Webster AR, and Michaelides M
- Subjects
- Humans, Male, Female, Adolescent, Child, Young Adult, Adult, Child, Preschool, Retina diagnostic imaging, Retina pathology, Infant, Mutation, Middle Aged, Retrospective Studies, Phenotype, Fluorescein Angiography methods, Cadherin Related Proteins, Usher Syndromes genetics, Usher Syndromes diagnosis, Usher Syndromes physiopathology, Electroretinography, Visual Acuity physiology, Tomography, Optical Coherence methods, Cadherins genetics
- Abstract
Purpose: The purpose of this study was to analyze the clinical spectrum and natural history of CDH23-associated Usher syndrome type ID (USH1D)., Methods: Molecularly-confirmed individuals had data extracted from medical records. Retinal imaging was extracted from an in-house database. The main outcome measurements were retinal imaging and electroretinography (ERG) and clinical findings, including age of onset, symptoms, best-corrected visual acuity (BCVA), outer nuclear layer (ONL) thickness, ellipsoid zone width (EZW), and hyperautofluorescent ring area., Results: Thirty-one patients were identified, harboring 40 variants in CDH23 (10 being novel). The mean (range, ±SD) age of symptom onset was 10.1 years (range = 1-18, SD = ±4.1). The most common visual symptoms at presentation were nyctalopia (93.5%) and peripheral vision difficulties (61.3%). The mean BCVA at baseline was 0.25 ± 0.22 in the right eyes and 0.35 ± 0.58 LogMAR in the left eyes. The mean annual loss rate in BCVA was 0.018 LogMAR/year over a mean follow-up of 9.5 years. Individuals harboring the c.5237G>A p.(Arg1746Gln) allele had retinitis pigmentosa (RP) sparing the superior retina. Seventy-seven percent of patients had hyperautofluorescent rings in fundus autofluorescence. Full-field and pattern ERGs indicated moderate-severe rod-cone or photoreceptor dysfunction with relative sparing of macular function in most patients tested. Optical coherence tomography (OCT) revealed intraretinal cysts in the transfoveal B-scan of 13 individuals (43.3%). The rate of EZW and ONL thickness loss was mild and suggestive of a wide window of macular preservation., Conclusions: Despite the early onset of symptoms, USH1D has a slowly progressive phenotype. There is high interocular symmetry across all parameters, making it an attractive target for novel therapies.
- Published
- 2024
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