Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Ophthalmology. 2012 Apr;119(4):819-26. doi: 10.1016/j.ophtha.2011.10.011. Epub 2012 Jan 20.
To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD).
Clinic-based, longitudinal, multicenter study.
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.
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.
The 10-year progression of all clinical parameters and cumulative lifetime risk of low vision and legal blindness were assessed.
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).
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.
评估 Cone 营养不良（CD）和 Cone-rod 营养不良（CRD）患者的临床病程、遗传病因和视觉预后。
基于诊所的、纵向的、多中心研究。
来自荷兰、比利时和英国不同眼科遗传诊所的连续 CD（N=98）、CRD（N=83）和受影响亲属（分别为 N=41 和 N=17）的先证者。
从医疗记录中登记了所有患者的最佳矫正视力、色觉、眼科检查、眼底照相、Goldmann 视野计和全视野标准视网膜电图（ERG）数据，平均随访 19 年。分别通过直接测序分析常染色体隐性（AR）和 X 连锁（XL）的 ABCA4、CNGB3、KCNV2、PDE6C 和 RPGR 基因。未对常染色体显性病例进行基因分型。
评估所有临床参数的 10 年进展和终身低视力和法定失明的累积风险。
CD 的平均发病年龄为 16 岁（标准差 11），CRD 为 12 岁（标准差 11；P=0.02）。92%的 CD 和 90%的 CRD 为 AR 遗传。诊断后 10 年，35%的 CD 和 51%的 CRD 出现靶心状黄斑病变；70%的 CRD 出现绝对周边视野缺损，37%的 CD 出现 ERG 杆状细胞受累。CD 的法定失明平均年龄为 48 岁（标准误差 [SE]，3.1），CRD 为 35 岁（SE，1.1；P<0.001）。在 8 例 AR-CD（9%）和 17 例 AR-CRD（26%）中发现 ABCA4 突变。在 CNGB3（3/90；3%）、KCNV2（4/90；4%）和 PDE6C（1/90；1%）中检测到其他突变。在 2 例 XL-CD 和 5 例（80%）XL-CRD 中发现 RPGR 基因突变。ABCA4 突变以及发病年龄<20 岁与视力丧失的快速进展显著相关（P<0.001）。
尽管 CD 的临床病程略优于 CRD，但两种疾病都会导致大多数患者失明。ABCA4 基因突变和疾病早发是视力丧失的独立预后参数。我们的数据可以为进展性 Cone 疾病患者提供咨询辅助。
