Genotypic and Phenotypic Characteristics of CRB1-Associated Retinal Dystrophies: A Long-Term Follow-up Study
Publication year
2017Source
Ophthalmology, 124, 6, (2017), pp. 884-895ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Human Genetics
Ophthalmology
Journal title
Ophthalmology
Volume
vol. 124
Issue
iss. 6
Page start
p. 884
Page end
p. 895
Subject
Radboudumc 12: Sensory disorders DCMN: Donders Center for Medical Neuroscience; Human Genetics Radboud University Medical Center; Ophthalmology Radboud University Medical CenterAbstract
PURPOSE: To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-five patients with CRB1-associated retinal dystrophies from 16 families. METHODS: A medical record review of 55 patients for age at onset, medical history, initial symptoms, best-corrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography (ffERG), Goldmann visual fields (VFs), and spectral-domain optical coherence tomography. MAIN OUTCOME MEASURES: Age at onset, visual acuity survival time, visual acuity decline rate, and electroretinography and imaging findings. RESULTS: A retinitis pigmentosa (RP) phenotype was present in 50 patients, 34 of whom were from a Dutch genetic isolate (GI), and 5 patients had a Leber congenital amaurosis phenotype. The mean follow-up time was 15.4 years (range, 0-55.5 years). For the RP patients, the median age at symptom onset was 4.0 years. In the RP group, median ages for reaching low vision, severe visual impairment, and blindness were 18, 32, and 44 years, respectively, with a visual acuity decline rate of 0.03 logarithm of the minimum angle of resolution per year. The presence of a truncating mutation did not alter the annual decline rate significantly (P = 0.75). Asymmetry in visual acuity was found in 31% of patients. The annual VF decline rate was 5% in patients from the genetic isolate, which was significantly faster than in non-GI patients (P < 0.05). Full-field electroretinography responses were extinguished in 50% of patients, were pathologically attenuated without a documented rod or cone predominance in 30% of patients, and showed a rod-cone dysfunction pattern in 20% of RP patients. Cystoid fluid collections in the macula were found in 50% of RP patients. CONCLUSIONS: Mutations in the CRB1 gene are associated with a spectrum of progressive retinal degeneration. Visual acuity survival analyses indicate that the optimal intervention window for subretinal gene therapy is within the first 2 to 3 decades of life.
This item appears in the following Collection(s)
- Academic publications [244262]
- Faculty of Medical Sciences [92892]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.