To describe the clinical characteristics, follow-up data and molecular genetic background in a large group of patients with central areolar choroidal dystrophy (CACD).
Retrospective case series study.
One hundred three patients with CACD from the Netherlands.
Ophthalmologic examination, including color vision testing, fundus photography, fluorescein angiography, fundus autofluorescence (FAF) imaging, optical coherence tomography, full-field electroretinography (ERG), multifocal ERG, and electrooculography. Blood samples were obtained for DNA extraction and subsequent analysis of the peripherin/RDS gene, as well as haplotype analysis.
Clinical characteristics, phenotypic range, clinical follow-up data, and FAF findings.
The mean age at onset of visual loss was 46 years, with subsequent gradual deterioration in visual acuity. Ninety-eight patients carried a p.Arg142Trp mutation in peripherin/RDS, whereas 5 affected members of a CACD family carried a p.Arg172Gln peripherin/RDS mutation. A remarkable variation in disease severity was observed, and nonpenetrance was seen up to the age of 64 years, in up to 21% of mutation carriers. However, most macular lesions in mutation carriers displayed a typical stage of CACD. Substantial changes were seen on FAF imaging after a mean follow-up period of 11 months. Electrophysiologic data were consistent with a central cone dystrophy. The age at onset and phenotypic characteristics of CACD show considerable overlap with atrophic age-related macular degeneration (AMD). The great majority of p.Arg142Trp-carrying CACD patients originated from the southeast region of the Netherlands, and haplotype analysis strongly suggested a common founder mutation.
When caused by a p.Arg142Trp mutation in the peripherin/RDS gene, CACD causes a central cone dystrophy phenotype. This mutation, which most likely originates from a common founder in most patients, is associated with a significant degree of nonpenetrance. In the elderly patient, CACD may be confused with AMD, especially in cases with decreased penetrance.
"Central areolar choroidal dystrophy should be considered because of the wide and well-circumscribed central patch of atrophy, that usually starts outside the fovea inside a hypopigmented area, and widens until it involves the whole macular area. Flecks are absent, but drusen-like lesions may be observed on fundus examination
. Both multifocal pattern dystrophy and central areolar choroidal dystrophy are associated with mutations of the PRPH2 gene with autosomal dominant inheritance. "
[Show abstract][Hide abstract] ABSTRACT: Background
The A3243G point mutation in mitochondrial DNA (mtDNA) is associated with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and MIDD syndromes (maternally inherited diabetes and deafness). Both MELAS and MIDD patients can present with visual symptoms due to a retinopathy, sometimes before the genetic diagnosis is made.
Patient 1: 46 year-old woman with diabetes mellitus and hearing loss was referred for an unspecified maculopathy detected during screening evaluation for diabetic retinopathy. Visual acuity was 20/20 in both eyes. Fundus examination showed bilateral macular and peripapillary hyperpigmented/depigmented areas.
Patient 2: 45 year-old woman was referred for recent vision loss in her left eye. History was remarkable for chronic fatigue, migraine and diffuse muscular pain. Visual acuity was 20/20 in her right eye and 20/30 in her left eye. Fundus exhibited several nummular perifoveal islands of retinal pigment epithelium atrophy and adjacent pale deposits in both eyes.
Retinal anatomy was investigated with autofluorescence, retinal angiography and optical coherence tomography. Retinal function was assessed with automated static perimetry, full-field and multifocal electroretinography and electro-oculography. Genetic testing of mtDNA identified a point mutation at the locus 3243.
Observation of RPE abnormalities in the context of suggestive systemic findings should prompt mtDNA testing.
[Show abstract][Hide abstract] ABSTRACT: Central areolar choroidal dystrophy (CACD) is a rare inherited disease, which causes progressive profound loss of vision in patients during their fourth decade. It is characterized by atrophy of retinal pigment epithelium, photoreceptors and choriocapillaris. The disease showed a genetic heterogeneity. Previously, mutations in the peripherin/RDS gene and a linkage to the CACD locus in the 17p13 region have been reported in CACD families. In this study, we report on a clinical and genetic investigation of CACD in a large Tunisian consanguineous family with 21 affected individuals in three living generations. CACD has been associated with drusen in some of them. Linkage analysis and mutational screening exclude linkage to the PRPH2/RDS gene and to the CACD locus. These data provide further evidence of the genetic heterogeneity of CACD.
Journal of Human Genetics 09/2009; 54(10):589-94. DOI:10.1038/jhg.2009.82 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A Chinese family with autosomal dominant central areolar choroidal dystrophy (CACD) was identified. The purpose of this study was to collect the clinical findings from the family and to identify the genetic entity by linkage analysis.
Forty-three individuals from 3 generations of the family underwent ophthalmologic examinations, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. Affected family members further underwent color vision test, color fundus photography, fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30 months. Peripheral venous blood or buccal swabs were collected from each family member and genomic DNA was extracted. Linkage analysis was performed for candidate genes or loci using microsatellite markers.
Seven family members in 3 continuous generations were diagnosed as having autosomal dominant CACD. The family showed progressive development of the disease, affecting both male and female. Age of onset of visual disturbances varied between 11 and 50 years. Phenotypic variability among affected individuals was apparent and ranged from relatively normal-appearing fundus with mild parafoveal pigment mottling to geographic atrophy of the macula. Fluorescein angiography showed hyperfluorescent parafoveal changes in early stage or well-demarcated area of chorioretinal atrophy with enhanced visibility of the residual underlying choroidal vessels in the late stage. Peripheral retina and visual fields were normal in affected individuals. Electroretinogram showed normal or mild reduction in the photopic amplitude. Eight candidate genes (STGD4, RCD1, peripherin/RDS, GUCA1A, RIMS1, UNC119, GUCY2D, and AIPL1) and two genetic loci (4p15.2 - 16.3, and 17p13) were excluded to be responsible for the disease by linkage analysis.
The clinical findings of this Chinese family with CACD shared similarities with previously reported families of other ethnicities. Linkage analysis excluded the known genes and genetic loci, indicating genetic heterogeneity of the disease.
Chinese medical journal 11/2009; 122(22):2686-90. · 1.05 Impact Factor
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