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Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy

Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy
Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy
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 than CRD, both disorders progressed to legal blindness in the majority of patients. Mutations in the ABCA4 gene and early onset of disease were independent prognostic parameters for visual loss. Our data may serve as an aid in counseling patients with progressive cone disorders.
819-826
Thiadens, Alberta A.H.J.
d614e63a-b794-49dd-a6a4-2def3b256c7e
Phan, T. My Lan
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Zekveld-Vroon, Renate C.
d9109fe9-854b-4a34-9b53-a3efccf4c43a
Leroy, Bart P.
2de8b1c0-7623-421b-871b-0f06c405e6ed
van den Born, L. Ingeborgh
f51e5125-7fce-4def-93df-45333ec5cb58
Hoyng, Carel B.
97ec7551-601c-449e-b539-5a476d56cd5d
Klaver, Caroline C.W.
bcfef58f-f6f3-4869-af44-c7ca68400797
Roosing, Susanne
8631ab57-2153-4d96-8167-ccaa12574ab5
Pott, Jan-Willem R.
50895809-5db7-4c5f-be90-00a3caae0c3e
van Schooneveld, Mary J.
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van Moll-Ramirez, Norka
c14b96d9-c56c-4d63-8b62-91e46519f8fb
van Genderen, Maria M.
326e9605-645d-401b-9a21-510d2a2163d0
Boon, Camiel J.F.
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den Hollander, Anneke I.
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Bergen, Arthur A.B.
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De Baere, Elfride
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Cremers, Frans P.M.
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Lotery, Andrew J.
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Thiadens, Alberta A.H.J.
d614e63a-b794-49dd-a6a4-2def3b256c7e
Phan, T. My Lan
7da7b8de-d615-44dc-8f2a-d61a3e014005
Zekveld-Vroon, Renate C.
d9109fe9-854b-4a34-9b53-a3efccf4c43a
Leroy, Bart P.
2de8b1c0-7623-421b-871b-0f06c405e6ed
van den Born, L. Ingeborgh
f51e5125-7fce-4def-93df-45333ec5cb58
Hoyng, Carel B.
97ec7551-601c-449e-b539-5a476d56cd5d
Klaver, Caroline C.W.
bcfef58f-f6f3-4869-af44-c7ca68400797
Roosing, Susanne
8631ab57-2153-4d96-8167-ccaa12574ab5
Pott, Jan-Willem R.
50895809-5db7-4c5f-be90-00a3caae0c3e
van Schooneveld, Mary J.
1668d2c6-4f21-4368-9647-c7169b9e0949
van Moll-Ramirez, Norka
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van Genderen, Maria M.
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Boon, Camiel J.F.
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den Hollander, Anneke I.
55961992-9080-4986-ae08-f3e680a49b11
Bergen, Arthur A.B.
befeadb8-1125-483d-8c02-51c5d362bd57
De Baere, Elfride
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Cremers, Frans P.M.
9ea95d37-7540-4486-97f1-d3aa57ce6f81
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514

Thiadens, Alberta A.H.J., Phan, T. My Lan, Zekveld-Vroon, Renate C., Leroy, Bart P., van den Born, L. Ingeborgh, Hoyng, Carel B., Klaver, Caroline C.W., Roosing, Susanne, Pott, Jan-Willem R., van Schooneveld, Mary J., van Moll-Ramirez, Norka, van Genderen, Maria M., Boon, Camiel J.F., den Hollander, Anneke I., Bergen, Arthur A.B., De Baere, Elfride, Cremers, Frans P.M. and Lotery, Andrew J. (2012) Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy. Ophthalmology, 119 (4), 819-826. (doi:10.1016/j.ophtha.2011.10.011). (PMID:22264887)

Record type: Article

Abstract

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 than CRD, both disorders progressed to legal blindness in the majority of patients. Mutations in the ABCA4 gene and early onset of disease were independent prognostic parameters for visual loss. Our data may serve as an aid in counseling patients with progressive cone disorders.

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More information

Published date: April 2012
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 359170
URI: http://eprints.soton.ac.uk/id/eprint/359170
PURE UUID: c605b5c0-71b1-448e-b94d-8b8ab49f26b9
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 23 Oct 2013 12:40
Last modified: 15 Mar 2024 03:16

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Contributors

Author: Alberta A.H.J. Thiadens
Author: T. My Lan Phan
Author: Renate C. Zekveld-Vroon
Author: Bart P. Leroy
Author: L. Ingeborgh van den Born
Author: Carel B. Hoyng
Author: Caroline C.W. Klaver
Author: Susanne Roosing
Author: Jan-Willem R. Pott
Author: Mary J. van Schooneveld
Author: Norka van Moll-Ramirez
Author: Maria M. van Genderen
Author: Camiel J.F. Boon
Author: Anneke I. den Hollander
Author: Arthur A.B. Bergen
Author: Elfride De Baere
Author: Frans P.M. Cremers

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