1. Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy
- Author
-
Thiadens, A.A., Phan, T.M., Zekveld-Vroon, R.C., Leroy, B.P., Born, L.I. van den, Hoyng, C.B., Klaver, C.C., Writing Committee for the Cone Disorders Study Group, C., Roosing, S., Pott, J.W., van Schooneveld, M.J., van Moll-Ramirez, N., van Genderen, M.M., Boon, C.J.F., Hollander, A.I. den, Bergen, A.A., De Baere, E., Cremers, F.P., Lotery, A.J., Thiadens, A.A., Phan, T.M., Zekveld-Vroon, R.C., Leroy, B.P., Born, L.I. van den, Hoyng, C.B., Klaver, C.C., Writing Committee for the Cone Disorders Study Group, C., Roosing, S., Pott, J.W., van Schooneveld, M.J., van Moll-Ramirez, N., van Genderen, M.M., Boon, C.J.F., Hollander, A.I. den, Bergen, A.A., De Baere, E., Cremers, F.P., and Lotery, A.J.
- Abstract
Item does not contain fulltext, OBJECTIVE: To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD). DESIGN: Clinic-based, longitudinal, multicenter study. PARTICIPANTS: Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N = 41 and N = 17, respectively) from various ophthalmogenetic clinics in The Netherlands, Belgium, and the United Kingdom. METHODS: Data on best-corrected Snellen visual acuity, color vision, ophthalmoscopy, fundus photography, Goldmann perimetry, and full-field standard electroretinogram (ERG) from all patients were registered from medical charts over a mean follow-up of 19 years. The ABCA4, CNGB3, KCNV2, PDE6C, and RPGR genes were analyzed by direct sequencing in autosomal recessive (AR) and X-linked (XL), respectively. Genotyping was not undertaken for autosomal-dominant cases. MAIN OUTCOME MEASURES: The 10-year progression of all clinical parameters and cumulative lifetime risk of low vision and legal blindness were assessed. RESULTS: The mean age onset for CD was 16 years (standard deviation, 11), and of CRD 12 years (standard deviation, 11; P = 0.02). The pattern of inheritance was AR in 92% of CD and 90% of CRD. Ten years after diagnosis, 35% of CD and 51% of CRD had a bull's eye maculopathy; 70% of CRD showed absolute peripheral visual field defects and 37% of CD developed rod involvement on ERG. The mean age of legal blindness was 48 (standard error [SE], 3.1) years in CD, and 35 (SE, 1.1; P<0.001) years in CRD. ABCA4 mutations were found in 8 of 90 (9%) of AR-CD, and in 17 of 65 (26%) of AR-CRD. Other mutations were detected in CNGB3 (3/90; 3%), KCNV2 (4/90; 4%), and in PDE6C (1/90; 1%). The RPGR gene was mutated in the 2 XL-CD and in 4 of 5 (80%) of XL-CRD. ABCA4 mutations as well as age of onset <20 years were significantly associated with a faster progression to legal blindness (P<0.001). CONCLUSIONS: Although CD had a slightly more favorable clinical course tha
- Published
- 2012