Central areolar choroidal dystrophy (CACD) is a hereditary disorder of the macula leading to a well-demarcated circumscribed area of atrophy of the pigment epithelium and choriocapillaris (Hoyng et al., 1996).
Sandvig (1955) described 13 cases of central areolar choroidal degeneration segregating in an autosomal dominant fashion over 4 generations of a family.
Wells et al. (1993) studied 3 families with macular dystrophy affecting predominantly the central retina, ...Sandvig (1955) described 13 cases of central areolar choroidal degeneration segregating in an autosomal dominant fashion over 4 generations of a family. Wells et al. (1993) studied 3 families with macular dystrophy affecting predominantly the central retina, in which affected individuals developed blurred central vision and photophobia in the third or fourth decade of life without night blindness or peripheral field loss. Funduscopic examination in the fifth decade of life showed sharply demarcated atrophy of the central retina, pigment epithelium, and choriocapillaris; patients had absolute central scotomata up to 20 degrees in size. Rod and cone thresholds at the border of the affected area were elevated, as were central color contrast sensitivities. Wroblewski et al. (1994) described in greater detail the clinical, psychophysical, and ERG findings in 2 of the families described by Wells et al. (1993). All affected members of these families had a progressive symmetric macular dystrophy. Symptoms of progressive central visual loss developed in the third or fourth decade of life, accompanied by central scotoma and well-demarcated atrophy of the retinal pigment epithelium (RPE) and choriocapillaris of the macula. Studies revealed absence of color-contrast sensitivity in the central visual field, with evidence of primary cone dysfunction and preservation of peripheral rod function. Hoyng et al. (1996) examined a total of 30 affected individuals from 7 families with CACD, who displayed fundal changes ranging from slight parafoveal depigmentation to the typical end stage, in which there is a well-demarcated area of atrophy of the pigment epithelium and choriocapillaris in the posterior pole. Hoyng et al. (1996) noted that in the patients with macular dystrophy studied by Wroblewski et al. (1994), the area of choroidal atrophy was larger than the area of atrophy found in CACD and severe vision loss developed before the age of 40 years, whereas in their own CACD patients, the atrophic macular lesions were smaller and not connected to the optic disc, and disabling vision loss generally developed only in the seventh decade, when the atrophy affected the fovea. Piguet et al. (1996) described a large family from the Zermatt area of Switzerland segregating autosomal dominant macular dystrophy, in which 24 of 42 members studied were affected. The severity of macular disease was clearly age-related and different stages of progression were identified, with adolescent patients showing central pigmentary alterations and patients in their late teens and twenties exhibiting drusen-like deposits. Later these defects formed focal areas of atrophy which eventually led to central geographic atrophy with severe visual loss by the fifth decade and cone-rod dysfunction. Piguet et al. (1996) stated that the clinical findings in this family were similar to those of the Spanish CACD family reported by Reig et al. (1995), and suggested that differences in electrophysiologic findings, which were normal in the latter family, might be due to differences in testing conditions. Piguet et al. (1996) designated the phenotype in the Swiss family 'Zermatt macular dystrophy.' Downes et al. (1999) examined 19 affected individuals from 12 British families with known mutation at codon 172 of the PRPH2 gene (Payne et al., 1998), including the family originally described by Chopdar (1993) and 2 of the families originally reported by Wells et al. (1993). Although the 12 families were referred with a variety of diagnoses, including CACD, macular dystrophy, retinitis pigmentosa (RP; see 608133), Sorsby fundus dystrophy (136900), cone dystrophy (180020), cone-rod dystrophy (see 120970), and Stargardt disease (248200), examination by Downes et al. (1999) revealed a distinctive common phenotype in 17 of the 19 patients, who exhibited a typical granular appearance of the RPE beginning in the third decade, with an initially central macular dystrophy extending to the temporal, superior, and inferior arcades by 50 years of age, with peripapillary extension with increasing age. Autofluorescence, fine matrix mapping, and pattern electroretinography (PERG) all showed abnormalities, even when patients were asymptomatic. Photopic and scotopic fields mirrored central losses, indicating anatomic loss of cones and rods corresponding to areas of decreased autofluorescence; areas of decreased sensitivity enlarged over time. The electrophysiologic assessment showed an abnormal, usually extinguished, PERG together with a normal full-field ERG, consistent with dysfunction confined to the macula without peripheral retinal involvement. Electrophysiologic findings in 2 of the patients differed markedly from those of the other 17, suggesting generalized rod and cone dysfunction with severe macular dysfunction. Yanagihashi et al. (2003) described a Japanese family with autosomal dominant CACD, in which affected individuals displayed sharply demarcated areas of chorioretinal atrophy in the macular and peripapillary regions, associated with small patchy areas of granular changes in the RPE around the fovea. Boon et al. (2009) studied 103 patients with CACD from 46 Dutch families and found that the mean age at onset of visual loss was 46 years, with subsequent gradual deterioration in visual acuity. Although 98 patients carried the R142W mutation in the PRPH2 gene (179605.0022), there was remarkable variation in disease severity, with nonpenetrance 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, and substantial changes were seen on fundus autofluorescence (FAF) imaging after a mean follow-up period of 11 months. Electrophysiologic data were consistent with a central cone dystrophy. Boon et al. (2009) noted that there is considerable phenotypic overlap between CACD and atrophic age-related macular degeneration (ARMD; see 603075), but stated that the drusen-like changes that may be observed at the edge of CACD lesions show intense FAF, whereas basal laminar drusen in ARMD generally do not, probably reflecting a difference in pathogenesis and composition of these drusen-like lesions despite the superficial similarity on ophthalmoscopy
In 18 patients from 4 families with the R172W mutation in the PRPH2 gene, Anand et al. (2009) plotted the total area of geographic atrophy as a function of age and collated visual acuity data from these patients with ...In 18 patients from 4 families with the R172W mutation in the PRPH2 gene, Anand et al. (2009) plotted the total area of geographic atrophy as a function of age and collated visual acuity data from these patients with previously published R172W cases to obtain age-related estimates of visual acuity; these data were then compared with published series of patients with the PRPH2 mutations R172Q and R142W. A trend was observed toward earlier age at onset and worse visual acuity with R172W compared to R142W or R172Q. Linear regression analysis showed that up to 60 years of age, visual acuity with the R172W mutation was significantly worse than that with the R142W (p less than 0.001) or R172Q (p = 0.04) mutations. A 'floor effect' on visual acuity was observed at age 60 years, with visual acuity thereafter being worse than 6/60 for most patients. Anand et al. (2009) suggested that the visual prognosis associated with variation in the PRPH2 gene may be mutation-specific and may be worse with the R172W mutation compared to the R142W or R172Q mutations
In 3 families with macular dystrophy involving the central retina, pigment epithelium, and choriocapillaris, Wells et al. (1993) screened the PRPH2 gene (179605) and identified 2 heterozygous missense mutations that segregated with disease in each family, respectively (R172Q, 179605.0006; ...In 3 families with macular dystrophy involving the central retina, pigment epithelium, and choriocapillaris, Wells et al. (1993) screened the PRPH2 gene (179605) and identified 2 heterozygous missense mutations that segregated with disease in each family, respectively (R172Q, 179605.0006; R172W, 179605.0007). In a Spanish family with CACD, Reig et al. (1995) analyzed the candidate gene PRPH2 and identified heterozygosity for the R172W mutation in affected individuals. In affected members from 7 families with CACD, Hoyng et al. (1996) identified heterozygosity for an R142W mutation (179605.0022) in the PRPH2 gene. They found no PRPH2 mutations in 4 sporadic CACD patients. Piguet et al. (1996) analyzed the PRPH2, rhodopsin (180380), and TIMP3 (188826) genes in a large Swiss pedigree segregating autosomal dominant progressive macular dystrophy and identified heterozygosity for the R172W mutation in the PRPH2 gene in affected individuals. Payne et al. (1998) identified the PRPH2 R172W mutation in 11 British families segregating autosomal dominant macular dystrophies, including 2 previously reported families (Wells et al., 1993 and Chopdar, 1993, respectively). Analysis of microsatellite markers revealed a shared haplotype that was absent in 50 population-matched controls, suggesting a founder effect. In 3 affected members of a Japanese family with autosomal dominant CACD, Yanagihashi et al. (2003) identified heterozygosity for a novel missense mutation in the PRPH2 gene (R195L; 179605.0021). Boon et al. (2009) analyzed the PRPH2 gene in 103 Dutch CACD patients and identified the R142W mutation in 98 patients from 45 different families and the R172Q mutation in 5 affected family members from 1 family. The great majority of R142W-carrying CACD patients originated from the southeast region of the Netherlands, and haplotype analysis suggested a common founder mutation