| #143200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| WAGNER SYNDROME 1; WGN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative titles; symbols | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| WAGNER VITREORETINAL DEGENERATION HYALOIDEORETINAL DEGENERATION OF WAGNER EROSIVE VITREORETINOPATHY; ERVR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinical Synopsis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| A number sign (#) is used with this entry because of evidence that the Wagner syndrome can be caused by heterozygous mutation in the gene encoding versican (VCAN; 118661), also known as chondroitin sulfate proteoglycan-2 (CSPG2), which is a proteoglycan present in the vitreous body of the eye. This finding helps in differentiation of the Wagner syndrome from Stickler syndrome (STL1; 108300), Marshall syndrome (154780), Weissenbacher-Zweymuller syndrome (277610), and other syndromes (see below) that have been distinguished with difficulty. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Features | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wagner (1938) described 13 members of a Canton Zurich family with a peculiar lesion of the vitreous and retina. Ten additional affected members were observed by Boehringer et al. (1960) and 5 more by Ricci (1961). In Holland Jansen (1962) described 2 families with a total of 39 affected persons. In addition to typical changes in the vitreous, retinal detachment occurs in some and cataract is another complication. See hyaloideotapetoretinal degeneration of Favre (268100). Irregular autosomal dominant inheritance was suggested by van Balen and Falger (1970) on the basis of 3 large pedigrees, and the syndromal association of cleft palate was emphasized. This disorder is, of course, a 'cause' of familial retinal detachment (Edmund, 1961). Graemiger et al. (1995) examined 60 members of the Swiss kindred originally studied by Wagner (1938). Twenty-eight members were found to be affected. The most consistent finding was an empty vitreous cavity with avascular strands or veils. Chorioretinal atrophy and cataract increased with age and occurred in all patients older than 45 years. Four patients had a history of a rhegmatogenous retinal detachment in 1 eye, which occurred at a median age of 20 years. Peripheral traction retinal detachments were found in 55% of eyes among patients older than 45 years. Glaucoma was present in 10 eyes (18%), 4 of which showed neovascular glaucoma. Of all patients, 63% showed elevated rod and cone thresholds on dark adaptation, and 87% showed subnormal b-wave amplitudes of the rod and cone systems on electroretinography. Thus, clinical expressivity of the disorder varied from unaffected carriers to bilateral blindness. Progression of the chorioretinal pathology was paralleled by electrophysiologic abnormalities. Miyamoto et al. (2005) studied a large Japanese family with Wagner syndrome. Ocular phenotypes of affected members included an empty vitreous with fibrillary condensations, avascular membrane, perivascular sheathing, and progressive chorioretinal dystrophy and were similar to those of the original Wagner syndrome family. All affected eyes examined exhibited pseudoexotropia with ectopic fovea. No systemic manifestations were observed. Wagner syndrome is often confused with Stickler syndrome (STL1; 108300) which is caused by mutations in the type II collagen gene (COL2A1; 120140). Like certain mutations in COL2A1 that result in a predominantly ocular or ocular-only phenotype, Wagner syndrome has no systemic features (Richards et al., 2006). However, the vitreoretinal phenotype is different, as neither of the recognized vitreous abnormalities in Stickler syndrome are present in Wagner syndrome and there is a lower incidence of retinal detachment. In addition, patients with Wagner syndrome have poor dark adaptation, which results in night blindness; this can be demonstrated by electrodiagnosis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mapping | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fryer et al. (1990) studied a large family with Wagner vitreoretinal degeneration but none of the nonocular features of Stickler syndrome. They demonstrated recombination with the COL2A1 locus (120140), thus excluding that gene as the site of the mutation. Brown et al. (1994) concluded that erosive vitreoretinopathy (ERVR) is very similar to Wagner disease. Brown et al. (1995) presented linkage evidence that erosive vitreoretinopathy and Wagner disease are allelic disorders, which are distinct from COL2A1-associated Stickler syndrome. Brown et al. (1995) demonstrated that ERVR and Wagner disease map to 5q13-q14. Black et al. (1999) reported a family in which multiple members through at least 4 generations suffered from a hereditary vitreoretinopathy associated with a variety of ocular developmental abnormalities, including posterior embryotoxon, congenital glaucoma, iris hypoplasia, congenital cataract, ectopia lentis, microphthalmia, and persistent hyperplastic primary vitreous. Genetic linkage studies mapped the disorder to markers from the proximal region of 5q13-q14, specifically to the 5-cM region between markers D5S626 and D5S2103. Both Wagner and erosive vitreoretinopathies had been mapped to the same region, suggesting that the condition in the family studied by Black et al. (1999) is allelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Molecular Genetics | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic linkage in the Japanese family described by Miyamoto et al. (2005) confirmed disease segregation with the previously identified WGN1 locus on 5q13-q14. Miyamoto et al. (2005) identified a heterozygous A-to-G transversion at the second base of the 3-prime acceptor splice site of intron 7 of the CSPG2 gene (118661.0001) that cosegregated with the disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| History | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Differentiation of the Wagner syndrome and the Stickler syndrome is difficult. Liberfarb et al. (1978, 1981) suggested that the syndromes of Wagner and Stickler are the same. They restudied 3 families reported by Hirose et al. (1973). Blair et al. (1979) reported the clinical and histopathologic findings in 3 severely diseased eyes from 3 patients in 2 families. They concluded that the Stickler and Wagner syndromes are the same disorder. One reason for hesitation in complete acceptance of identity of the Wagner and Stickler syndromes is the fact that retinal detachment was not noted in any of the 28 members of the original Swiss family studied by Wagner (1938) and later by Boehringer et al. (1960) and Ricci (1961). Korkko et al. (1993) noted phenotypic similarity to the family described by Wagner (1938) in a family in which they found a COL2A1 mutation (120140.0014). The family had early-onset cataracts, lattice degeneration of the retina, and retinal detachment with no involvement of nonocular tissues. Miyamoto et al. (2005) classified the family of Korkko et al. (1993) as an example of Stickler syndrome. Richards et al. (2006) suggested that the family of Korkko et al. (1993) could be an example of predominantly ocular Stickler syndrome or dominantly inherited rhegmatogenous retinal detachment. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| See Also: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bundey and Leffler (1974) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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