Alternative titles; symbols
SNOMEDCT: 724384008; ORPHA: 86813; DO: 0111228;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11p15.3 | Sveinsson chorioretinal atrophy | 108985 | Autosomal dominant | 3 | TEAD1 | 189967 |
A number sign (#) is used with this entry because of evidence that Sveinsson chorioretinal atrophy (SCRA) is caused by heterozygous mutation in the TEA domain family member-1 gene (TEAD1; 189967) on chromosome 11p15.
Sveinsson chorioretinal atrophy (SCRA) is characterized by bilateral, well-defined, tongue-shaped strips of atrophic retina and choroid that extend from the optic nerve into the peripheral ocular fundus. The lesions may be evident at birth and usually progress at a variable rate, sometimes leading to central visual loss. Separate small distinct circular atrophic lesions are observed in the peripheral ocular fundus in some patients. Congenital anterior polar cataracts are found in approximately 25% of affected individuals (summary by Jonasson et al., 2007).
Sveinsson (1939) first described this disorder in an Icelandic mother and son. The fundus showed peripapillary chorioretinal atrophy with wide tongue-shaped extensions to the periphery having no connection with the retinal vessels. He referred to the condition as 'chorioiditis areata' but later recognized the inappropriateness of this designation since there was no inflammation. In a follow-up of this family, Sveinsson (1979) found a total of 13 affected persons (6 male and 7 female) in 4 generations with at least 3 instances of male-to-male transmission. Sveinsson saw his patients in Reykjavik.
Magnusson (1981), who used the designation 'atrophia areata' for this disorder, observed 38 patients in the northern part of Iceland. One pedigree contained 26 of these patients; the other 12 came from the same district. The pedigree with 26 affected showed no instance of male-to-male transmission. Magnusson (1981) stated that the atrophy is slowly progressive, most likely beginning in the retinal pigment epithelium (RPE), and that usually there is combined myopia and astigmatism.
Franceschetti (1962) reviewed comprehensively the peripapillary atrophies and classified this Icelandic form in a category he called helicoid peripapillar chorioretinal degeneration.
Fossdal et al. (2004) noted reports describing patients with atrophia areata in Iceland, Switzerland, and Canada. They also stated that they had received personal communications describing patients with this condition in the Faroe Islands, Denmark, Germany, Norway, Sweden, U.K., and U.S. These patients all had Icelandic ancestors and were members of the extended ancestral pedigree described in their report (Fossdal et al., 2004). The vast majority of reported cases, and the only reports describing autosomal dominant inheritance, were Icelandic.
Fossdal et al. (2004) reported a registry of 116 living Icelandic patients at the time of their report. Of this registry they studied 81 patients and 107 relatives and spouses. Genotyping with microsatellite markers revealed that all but 3 of the 81 patients could be traced to a male founder born in 1540. The 3 patients without detectable connection to the founder, a father and his 2 children, were shown to constitute a separate family.
Jonasson et al. (2007) reported the histopathologic features in an eye from a patient with clinically and genetically confirmed Sveinsson chorioretinal atrophy. In the most advanced areas of chorioretinal atrophy, the sensory retina, retinal pigment epithelium, choriocapillaris, and choroid were absent. In the transition between affected and unaffected areas, only the RPE and the outer segments of the photoreceptors were affected. The optic nerve was smaller than normal but well myelinated. Other ocular tissues retained a relatively normal appearance. Jonasson et al. (2007) concluded that the mildest and presumably earliest morphologic changes of SCRA involved the photoreceptor outer segments, the RPE, and choriocapillaris.
Milenkovic et al. (2005) described a Serbian family with helicoid peripapillary degeneration. The 20-year-old daughter had been diagnosed at age 10 years after she presented with visual disturbances. She and her 15-year-old brother had mild reductions in visual acuity (20/30 to 20/40) whereas their father had 20/20 vision. All 3 had discrete cataracts in the anterior lens and normal intraocular pressures. Funduscopy showed helicoid peripapillary chorioretinal atrophy in both sibs, whereas their father had only slight irregularities in color and pigmentation around the optic disc. However, fluorescein angiography revealed bilateral helicoidal peripapillary lesions in the father as well as in the sibs.
The transmission pattern of SCRA in the large Icelandic family reported by Fossdal et al. (2004) was consistent with autosomal dominant inheritance.
The question of autosomal dominant versus X-linked dominant inheritance was settled by the demonstration of linkage to 11p15 by Fossdal et al. (1995). In the course of a genome linkage search with 112 microsatellite DNA markers, Fossdal et al. (1995) found that D11S1323 and D11S902 on 11p15 flanked the region encompassing the AA gene.
Using crossover analysis, Fossdal et al. (2004) identified a 593-kb segment shared by all atrophia areata patients within the large Icelandic pedigree they studied. Sequencing exons of the only gene in this interval, the transcriptional enhancer TEAD1 (189967), revealed a novel missense mutation (Y421H; 189967.0001) carried by all patients and none of the 502 controls. The mutation occurs in a conserved amino acid sequence in the C terminal of the protein, a potential binding site for YAP65 (YAP1; 606608), one of the cofactors of TEAD1 that is coexpressed in human retina.
By sequencing genomic DNA from a Serbian father and 2 children with Sveinsson chorioretinal atrophy, who were originally reported by Milenkovic et al. (2005), Grubisa et al. (2021) identified heterozygosity for a missense mutation in the TEAD1 gene (Y421N; 189967.0002), which they noted was at the same position as the recurrent Icelandic variant. The authors suggested that Y421 represents a mutational hotspot.
Fossdal et al. (2004) reviewed the nomenclature of this disorder and proposed that it should be called Sveinsson chorioretinal atrophy (SCRA).
Fossdal, R., Jonasson, F., Kristjansdottir, G. T., Kong, A., Stefansson, H., Gosh, S., Gulcher, J. R., Stefansson, K. A novel TEAD1 mutation is the causative allele in Sveinsson's chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration). Hum. Molec. Genet. 13: 975-981, 2004. [PubMed: 15016762] [Full Text: https://doi.org/10.1093/hmg/ddh106]
Fossdal, R., Magnusson, L., Weber, J. L., Jensson, O. Mapping the locus of atrophia areata, a helicoid peripapillary chorioretinal degeneration with autosomal dominant inheritance, to chromosome 11p15. Hum. Molec. Genet. 4: 479-483, 1995. [PubMed: 7795606] [Full Text: https://doi.org/10.1093/hmg/4.3.479]
Franceschetti, A. A curious affection of the fundus oculi: helicoid peripapillar chorioretinal degeneration. Its relation to pigmentary paravenous chorioretinal degeneration. Doc. Ophthal. 16: 81-110, 1962. [PubMed: 13959112] [Full Text: https://doi.org/10.1007/BF00146721]
Grubisa, I., Jankovic, M., Nikolic, N., Jaksic, V., Risimic, D., Mavija, M., Stamenkovic, M., Zlatovic, M., Milasin, J. Novel TEAD1 gene variant in a Serbian family with Sveinsson's chorioretinal atrophy. Exp. Eye Res. 207: 108575, 2021. [PubMed: 33864784] [Full Text: https://doi.org/10.1016/j.exer.2021.108575]
Jonasson, F., Hardarson, S., Olafsson, B. M., Klintworth, G. K. Sveinsson chorioretinal atrophy/helicoid peripapillary chorioretinal degeneration: first histopathological report. Ophthalmology 114: 1541-1546, 2007. [PubMed: 17339054] [Full Text: https://doi.org/10.1016/j.ophtha.2006.11.016]
Magnusson, L. Atrophia areata: a variant of peripapillary chorioretinal degeneration. Acta Ophthal. 59: 659-664, 1981. [PubMed: 7315221] [Full Text: https://doi.org/10.1111/j.1755-3768.1981.tb08731.x]
Milenkovic, S., Kosanovic-Jakovic, N., Djuric, S., Risimic, D., Ivancevic-Milenkovic, M. Helicoidal peripapillary degeneration. Eye (Lond) 19: 917-920, 2005. [PubMed: 15359244] [Full Text: https://doi.org/10.1038/sj.eye.6701670]
Sveinsson, K. Chorioiditis areata. Acta Ophthal. 17: 73-80, 1939.
Sveinsson, K. Helicoidal peripapillary chorioretinal degeneration. Acta Ophthal. 57: 69-75, 1979. [PubMed: 419979] [Full Text: https://doi.org/10.1111/j.1755-3768.1979.tb06661.x]