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.