Alternative titles; symbolsCHOROIDAL DYSTROPHY, CENTRAL AREOLAR; CACDCHOROIDAL SCLEROSIS▼ DescriptionCentral areolar choroidal dystrophy (CACD) is a hereditary r...
Alternative titles; symbols
Central areolar choroidal dystrophy (CACD) is a hereditary retinal disorder that principally affects the macula, often resulting in a well-defined area of atrophy of the retinal pigment epithelium (RPE) and choriocapillaris in the center of the macula. Dysfunction of macular photoreceptors usually leads to a decrease in visual acuity, generally occurring between the ages of 30 and 60 years (summary by Boon et al., 2009).
Genetic Heterogeneity of Central Areolar Choroidal Dystrophy
CACD2 (613105) is caused by mutation in the PRPH2 gene (179605) on chromosome 6p21. See also CACD3 (613144) for a family in which linkage to the PRPH2 gene and chromosome 17p13 has been excluded.
▼ Clinical Features
Waardenburg (1952) described central choroidal sclerosis in 2 daughters of a first-cousin marriage. Many others have reported sibs with central choroidal sclerosis and several instances of parental consanguinity are on record (e.g., Sorsby and Crick, 1953). Krill and Archer (1971) described brother and sister with choriocapillaris atrophy throughout most of the posterior eyegrounds.
Lotery et al. (1996) reported a large Northern Irish pedigree in which 19 individuals in 3 generations had central areolar choroidal dystrophy. CACD diagnosis was based on ophthalmic examination including stereo fundus photography, fluorescein angiography, and electrophysiologic testing. The family showed an autosomal dominant inheritance pattern. Linkage to the PRPH2 (179605), ROM1 (180721), RHO (180380), and PDE6B (180072) genes had previously been excluded.
Chen et al. (2017) studied a large Chinese family with GUCA1A (600364)-associated retinal dystrophy (COD3; 602093) in which 18 affected individuals exhibited phenotypes ranging from mild photoreceptor degeneration to CACD. Noting that GUCA1A and the CACD-associated genes GUCY2D and PRPH2 are all expressed exclusively in photoreceptors, Chen et al. (2017) suggested that the changes observed in the RPE and choriocapillaris in patients given a clinical diagnosis of CACD are likely secondary to photoreceptor dystrophy.
By genomewide linkage analysis in a large Northern Irish pedigree with CACD, Lotery et al. (1996) established linkage of the disorder in this family to chromosome 17p13 (maximum lod = 4.7 at theta = 0.0 with D17S796). No mutation in the coding region of the PITPN gene (600174) was identified. In the same family, Hughes et al. (1998) refined the critical region to an interval of approximately 2.4 Mb (5 cM) flanked by polymorphic markers D17S1810 and CHLC GATA7B03 on chromosome 17p13.
▼ Molecular Genetics
In the Irish family with CACD mapping to chromosome 17p13, originally reported by Lotery et al. (1996), Hughes et al. (2012) performed massively parallel sequencing in the region of linkage and identified a heterozygous missense mutation in the GUCY2D gene (V933A; 600179.0011) that segregated with disease and was not found in 7 control samples or in the 1000 Genomes Project database.