Alternative titles; symbols
ORPHA: 99001; DO: 0060866;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6p21.1 | Macular dystrophy, patterned, 1 | 169150 | Autosomal dominant | 3 | PRPH2 | 179605 |
A number sign (#) is used with this entry because of evidence that patterned macular dystrophy-1 (MDPT1) is caused by heterozygous mutation in the photoreceptor peripherin gene (PRPH2; 179605) on chromosome 6p21.
Patterned dystrophies of the retinal pigment epithelium (RPE) refer to a heterogeneous group of macular disorders, characterized by an abnormal accumulation of lipofuscin in the RPE. The lipofuscin is most apparent in the macular area, and its distribution can show various sizes and shapes. High inter- and intrafamilial variability has been described, and retinitis pigmentosa (RP; see 268000)-like changes have sometimes been observed in association with patterned dystrophies (summary by Vaclavik et al., 2012).
Three main varieties of patterned dystrophy of the RPE have been described: reticular ('fishnet-like') dystrophy (see 179840 and 267800), macroreticular ('spider-shaped') dystrophy, and butterfly-shaped pigment dystrophy of the fovea.
Genetic Heterogeneity of Patterned Macular Dystrophy
Also see MDPT2 (608970), caused by mutation in the CTNNA1 gene (116805) on chromosome 5q31; and MDPT3 (617111), caused by mutation in the MAPKAPK3 gene (602130) on chromosome 3p21.
Hsieh et al. (1977) described a family in which the mother had probable reticular dystrophy, whereas a daughter had macroreticular dystrophy and a son had butterfly-shaped pigment dystrophy. They questioned the previously assumed distinctness. Marmor and Byers (1977) reported 3 generations of a family with alterations in the RPE. Younger members had granular pigment dispersed beneath the fovea, while older members showed a reticular pigment pattern, similar to other pigment dystrophies.
Watzke et al. (1982) reported 2 pedigrees with pattern dystrophy. They noted that onset was usually in the second or third decade with great phenotypic variability. De Jong and Delleman (1982) described 1 family with 3 different manifestations of pigment epithelial pattern dystrophy: butterfly dystrophy, reticular dystrophy, and fundus pulverulentus. All led to the same results with regard to visual acuity, visual fields, dark adaptation, electroretinogram (ERG), and electrooculogram. Inheritance was autosomal dominant. The authors suggested that the phenotypes are different expressions of the same pigment epithelial dystrophy.
Giuffre and Lodato (1986) reported 3 sibs with different phenotypes. The first sib had macroreticular dystrophy associated with butterfly-shaped dystrophy in one eye and with vitelliform cyst in the other eye. The second sib showed the atrophic outcome of a vitelliform cyst with development of subretinal neovascular membranes in one eye, and a radial pigmented macular dystrophy in the other eye. The third sib had bilateral macular vitelliform lesions.
Kim et al. (1995) examined 6 affected individuals over 2 generations of a large family with fundus findings consistent with patterned dystrophy of the macula. Abnormalities ranged from subtle RPE pigmentary changes with loss of the foveal reflex to widespread macular pigmentary changes and yellow deposits in the RPE associated with disciform scarring. Only 2 patients had decreased vision unilaterally due to disciform scarring, whereas the remainder were asymptomatic. Ophthalmoscopically, the peripheral retina appeared normal in all patients, but fluorescein angiography revealed a dark choroid in 2 and choroidal neovascularization in 1. On ERG, 3 patients showed normal responses, whereas 2 others showed low amplitude responses suggestive of widespread retinal dysfunction. Color contrast sensitivity testing revealed a tritan defect of varying severity in all 5 individuals and, in some, an additional mild protan defect.
Daniele et al. (1996) reported 2 families in which affected members showed different patterned alterations in the RPE, suggesting that a single pathogenic mechanism is involved in several forms.
Yang et al. (2004) studied a family in which 4 affected individuals spanning 2 generations had patterned macular dystrophy. The proband was a 31-year-old man with mild metamorphopsia and visual acuity of 20/25 bilaterally. Funduscopy showed a butterfly-shaped pattern dystrophy characterized by the subretinal accumulation of yellow material in the macular area. Fluorescein angiography showed typical central hypofluorescence surrounded by areas of hyperfluorescence. His 69-year-old father and a 30-year-old sister, who had no visual complaints and 20/20 vision bilaterally, showed similar findings on funduscopic examination and fluorescein angiography. An asymptomatic 29-year-old sister, whose visual acuity was 20/20 bilaterally, had a depigmented spot in the center of the fovea on funduscopy as well as a mild central hyperfluorescent defect that faded in late frames on fluorescein angiography.
Vaclavik et al. (2012) described a Swiss family with patterned macular dystrophy in which 8 affected individuals spanning 3 generations exhibited high intrafamilial variability as well as variability between both eyes of the same patient. The proband was asymptomatic at age 41 years when ophthalmologic examination revealed bilateral irregular yellowish flecks in the posterior pole and bilateral foveal butterfly-shaped lesions; she was diagnosed as having multifocal patterned dystrophy simulating Stargardt disease (see 248200). At age 48, she had metamorphopsia, photophobia, and night blindness, and optical coherence tomography (OCT) showed subfoveal hyperreflective material consistent with choroidal neovascularization. The neovascularization regressed after 4 intravitreal injections of the anti-VEGF (192240) monoclonal antibody ranibizumab. The proband's 25-year-old daughter experienced night blindness, but examination demonstrated a normal retina by funduscopy and autofluorescence imaging. Full-field ERG showed a mild reduction in rod response. The proband's 43-year-old male cousin reported metamorphopsia and was found to have butterfly-pattern dystrophy in 1 eye and adult-onset foveomacular dystrophy (AOFMD; 608161) in the other. Other affected individuals in this family had been given diagnoses of 'early' or 'atrophic' age-related macular degeneration (ARMD; see 603075).
In a family in which 4 affected individuals spanning 2 generations had patterned macular dystrophy, Yang et al. (2004) performed genotype analysis using the short tandem-repeat polymorphism DNA markers D6S400, D6S1582, and D6S2410 and found linkage to the RDS/peripherin locus.
The transmission pattern of MDPT1 in the families reported by Nichols et al. (1993, 1993) was consistent with autosomal dominant inheritance.
In affected members of families segregating butterfly dystrophy of the RPE, Nichols et al. (1993, 1993) identified heterozygous mutations in the PRPH2 gene (179605.0009-179605.0010).
In 6 affected individuals over 2 generations of a large family with fundus findings consistent with patterned dystrophy of the macula, Kim et al. (1995) identified heterozygosity for a 4-bp insertion in the PRPH2 gene (179605.0013). The mutation was not found in 6 unaffected family members.
In a patient diagnosed with patterned macular dystrophy, Payne et al. (1998) identified heterozygosity for a missense mutation in the PRPH2 gene (C213R; 179605.0023).
In a family in which 4 affected individuals spanning 2 generations had patterned macular dystrophy mapping to the RDS/peripherin locus, Yang et al. (2004) sequenced the RDS gene and identified a heterozygous missense mutation (Y141C; 179605.0024) that segregated with disease in the family and was not found in 200 control chromosomes. Yang et al. (2004) also identified the Y141C mutation in affected members of 2 unrelated families with adult-onset foveomacular dystrophy (AOFMD; 608161). Haplotype analysis was consistent with an ancestral founder mutation in all 3 families. The authors stated that it was unclear why the Y141C mutation caused patterned macular dystrophy in 1 family and AOFMD in the other 2, and suggested that genetic modifiers or environmental influences may play a role in these phenotypic differences.
In affected individuals from a Swiss family with patterned macular dystrophy who exhibited marked intrafamilial and even intraindividual phenotypic variability, Vaclavik et al. (2012) identified heterozygosity for the Y141C mutation in the RDS gene.
Wang et al. (2013) identified the C213R mutation in homozygosity in a 29-year-old woman diagnosed with Leber congenital amaurosis (LCA18; see 608133); the mutation was also detected in heterozygosity in 2 family members who exhibited patterned macular dystrophy: the proband's asymptomatic 57-year-old mother, who had 20/20 visual acuity, showed florid butterfly-shaped macular pattern dystrophy as well as other retinal flecks; and her 7-year-old son, who had decreased visual acuity due to partial amblyopia, showed a miniature form of foveal butterfly-shaped macular pattern dystrophy. In another family, a 30-year-old woman with juvenile retinitis pigmentosa (see 608133) was homozygous for an L185P mutation in PRPH2 (179605.0004), whereas her asymptomatic 56-year-old father, who had normal visual acuity but patterned macular dystrophy and foveal changes on examination, was heterozygous for L185P.
Daniele, S., Carbonara, A., Daniele, C., Restagno, G., Orcidi, F. Pattern dystrophies of the retinal pigment epithelium. Acta Ophthal. Scand. 74: 51-55, 1996. [PubMed: 8689482] [Full Text: https://doi.org/10.1111/j.1600-0420.1996.tb00682.x]
de Jong, P. T. V. M., Delleman, J. W. Pigment epithelial pattern dystrophy: four different manifestations in a family. Arch. Ophthal. 100: 1416-1421, 1982. [PubMed: 7115165] [Full Text: https://doi.org/10.1001/archopht.1982.01030040394003]
Giuffre, G., Lodato, G. Vitelliform dystrophy and pattern dystrophy of the retinal pigment epithelium: concomitant presence in a family. Brit. J. Ophthal. 70: 526-532, 1986. [PubMed: 3718916] [Full Text: https://doi.org/10.1136/bjo.70.7.526]
Hsieh, R. C., Fine, B. S., Lyons, J. S. Patterned dystrophies of the retinal pigment epithelium. Arch. Ophthal. 95: 429-435, 1977. [PubMed: 843272] [Full Text: https://doi.org/10.1001/archopht.1977.04450030071006]
Kim, R. Y., Dollfus, H., Keen, T. J., Fitzke, F. W., Arden, G. B., Bhattacharya, S. S., Bird, A. C. Autosomal dominant pattern dystrophy of the retina associated with a 4-base pair insertion at codon 140 in the peripherin/RDS gene. Arch. Ophthal. 113: 451-455, 1995. [PubMed: 7710395] [Full Text: https://doi.org/10.1001/archopht.1995.01100040067029]
Marmor, M. F., Byers, B. Pattern dystrophy of the pigment epithelium. Am. J. Ophthal. 84: 32-44, 1977. [PubMed: 900215] [Full Text: https://doi.org/10.1016/0002-9394(77)90320-8]
Nichols, B. E., Drack, A. V., Vandenburgh, K., Kimura, A. E., Sheffield, V. C., Stone, E. M. A 2 base pair deletion in the RDS gene associated with butterfly-shaped pigment dystrophy of the fovea. Hum. Molec. Genet. 2: 601-603, 1993. Note: Erratum: Hum. Molec. Genet. 2: 1347 only, 1993. [PubMed: 8251014] [Full Text: https://doi.org/10.1093/hmg/2.5.601]
Nichols, B. E., Sheffield, V. C., Vandenburgh, K., Drack, A. V., Kimura, A. E., Stone, E. M. Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene. Nature Genet. 3: 202-207, 1993. [PubMed: 8485574] [Full Text: https://doi.org/10.1038/ng0393-202]
Payne, A. M., Downes, S. M., Bessant, D. A. R., Bird, A. C., Bhattacharya, S. S. Founder effect, seen in the British population, of the 172 peripherin/RDS mutation--and further refinement of genetic positioning of the peripherin/RDS gene. (Letter) Am. J. Hum. Genet. 62: 192-195, 1998. [PubMed: 9443872] [Full Text: https://doi.org/10.1086/301679]
Vaclavik, V., Tran, H. V., Gaillard, M.-C., Schorderet, D. F., Munier, F. L. Pattern dystrophy with high intrafamilial variability associated with Y141C mutation in the peripherin/RDS gene and successful treatment of subfoveal CNV related to multifocal pattern type with anti-VEGF (ranibizumab) intravitreal injections. Retina 32: 1942-1949, 2012. [PubMed: 22466463] [Full Text: https://doi.org/10.1097/IAE.0b013e31824b32e4]
Wang, X., Wang, H., Sun, V., Tuan, H.-F., Keser, V., Wang, K., Ren, H., Lopez, I., Zaneveld, J. E., Siddiqui, S., Bowles, S., Khan, A., and 12 others. Comprehensive molecular diagnosis of 179 Leber congenital amaurosis and juvenile retinitis pigmentosa patients by targeted next generation sequencing. J. Med. Genet. 50: 674-688, 2013. [PubMed: 23847139] [Full Text: https://doi.org/10.1136/jmedgenet-2013-101558]
Watzke, R. C., Folk, J. C., Lang, R. M. Pattern dystrophy of the retinal pigment epithelium. Ophthalmology 89: 1400-1406, 1982. [PubMed: 6984500] [Full Text: https://doi.org/10.1016/s0161-6420(82)34632-1]
Yang, Z., Li, Y., Jiang, L., Karan, G., Moshfeghi, D. M., O'Connor, S. T., Li, X., Yu, Z., Lewis, H., Zack, D. J., Jacobson, S. G., Zhang, K. A novel RDS/peripherin gene mutation associated with diverse macular phenotypes. Ophthalmic Genet. 25: 133-145, 2004. [PubMed: 15370544] [Full Text: https://doi.org/10.1080/13816810490514388]