Sveinsson Chorioretinal Atrophy

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 (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.

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.

Fossdal et al. (2004) reviewed the nomenclature of this disorder and proposed that it should be called Sveinsson chorioretinal atrophy (SCRA).