Clinical Course, Genetic Etiology, and Visual Outcome in Cone and Cone-Rod Dystrophy

详细信息    查看全文

• 作者：Alberta A.H.J. Thiadens ; MD ; PhD¹ ; ² ; ^?/sup> ; T. My Lan Phan ; MD³ ; Renate C. Zekveld-Vroon ; MD⁴ ; Bart P. Leroy ; MD ; PhD⁵ ; L. Ingeborgh van den Born ; MD ; PhD⁶ ; Carel B. Hoyng ; MD ; PhD³ ; Caroline C.W. Klaver ; MD ; PhD¹ ; ⁷ ; ^{c.c.w.klaver@erasmusmc.nl} ; Writing Committee for the Cone Disorders Study Group Consortium ; Susanne Roosing² ; ⁸ ; Jan-Willem R. Pott⁹ ; Mary J. van Schooneveld⁴ ; ¹⁰ ; Norka van Moll-Ramirez¹¹ ; Maria M. van Genderen¹² ; Camiel J.F. Boon³ ; Anneke I. den Hollander² ; ³ ; ⁸ ; Arthur A.B. Bergen⁴ ; ¹³ ; Elfride De Baere⁵ ; Frans P.M. Cremers² ; ⁸ ; Andrew J. Lotery¹⁴
• 刊名：Ophthalmology
• 出版年：2012
• 出版时间：April, 2012
• 年：2012
• 卷：119
• 期：4
• 页码：819-826
• 全文大小：626 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

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.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.