Differential Diagnosis of Wagner Syndrome

Syndromes with overlapping features

A recent review summarizes the clinical features of inherited vitreoretinopathies and points out the importance of consulting an expert ophthalmologist in diagnostic assessment of the disease .

Autosomal dominant vitreoretinopathies

Snowflake vitreoretinal degeneration (SVD) (OMIM 193230). Both SVD and VCAN-related vitreoretinopathy exhibit vitreous abnormalities including fibrillar condensation, gel liquefaction, and marked thickening of the cortical vitreous. In SVD, however, membranous degeneration of the vitreous with avascular strands and veils is not observed. Retinal defects start in the superficial retinal layers, whereas in VCAN-related vitreoretinopathy they start in the deep retinal layers and choroid; retinal detachment is uncommon; and the retinal crystalline snowflake-like deposits that give the disease its name are common. Mutations in KCNJ13 are causative .

Stickler syndrome (OMIM 108300, 184840, 604841). Stickler syndrome, or hereditary arthroophthalmopathy, is most often a systemic disorder associated with a skeletal dysplasia (spondyloepiphyseal dysplasia) and craniofacial abnormalities, including cleft palate. Retinal detachment is much more common in Stickler syndrome (50%) than in VCAN-related vitreoretinopathy (15%). Abnormal dark adaptation associated with alterations in the ERG that is common in VCAN-related vitreoretinopathy has not been described in Stickler syndrome. Two different and specific

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Clinical Description of Wagner's Disease

Natural History

VCAN-related vitreoretinopathy comprises the phenotypic continuum of Wagner vitreoretinal degeneration (Wagner syndrome) and erosive vitreoretinopathy (ERVR), two disorders that were previously thought to be distinct entities based on clinical findings. Wagner syndrome, the first reported inherited vitreoretinal degeneration, was described by Wagner . ERVR was described in 1994 as a new clinical entity with some features that overlapped with Wagner syndrome .

Vitreoretinal degeneration

As described by Wagner , the hallmark of VCAN-related vitreoretinopathy is progressive degenerative changes of the vitreous (syneresis) and the vitreoretinal interface beginning at a young age. Syneresis can lead to massive liquefaction of the vitreous such that on slit-lamp examination the vitreous cavity appears optically empty ("empty vitreous") with pockets of liquefied vitreous that are usually lined by avascular strands and veils. Preretinal vitreous membranes that span the whole equator of the eye are characteristic. Ocular changes show considerable inter- and intrafamilial variability.

The first signs usually become apparent during early adolescence, but onset can be as early as age two years .

No gender-specific difference in the occurrence or frequency of any particular ocular features has been observed.

The vitreous degeneration, which is assumed to be the primary pathology, leads to a number of secondary changes, including presenile cataract,

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Wagner Vitreoretinal Degeneration

Wagner Vitreoretinal Degeneration (Wagner Syndrome), Erosive Vitreoretinopathy (ERVR)

Disease characteristics. VCAN-related vitreoretinopathy, which includes Wagner syndrome and erosive vitreoretinopathy (ERVR), is characterized by “optically empty vitreous” on slit-lamp examination and avascular vitreous strands and veils, mild or occasionally moderate to severe myopia, presenile cataract, night blindness of variable degree associated with progressive chorioretinal atrophy, retinal detachment at advanced stages of the disease, and reduced visual acuity. Systemic abnormalities are not observed. The first signs usually become apparent during early adolescence, but onset can be as early as age two years.

Diagnosis/testing. The clinical diagnosis of VCAN-related vitreoretinopathy is established based on typical clinical findings and a family history consistent with autosomal dominant inheritance. VCAN (previously CSPG2) is the only gene known to be associated with Wagner syndrome and ERVR. Molecular genetic testing is available on a clinical basis.

Management. Treatment of manifestations: Refractive error is corrected by spectacles or contact lenses; visually disabling cataract is treated by cataract surgery, preferably by an experienced surgeon. Retinal breaks without retinal detachment are treated with laser retinopexy or cryocoagulation. Vitreoretinal surgery is indicated for retinal detachment, vitreoretinal traction involving the macula, or epiretinal membranes

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Diagnosis of Wagner's Disease

Clinical Diagnosis of Wagner Syndrome

VCAN-related vitreoretinopathy is characterized by:

“Optically empty vitreous” on slit-lamp examination and avascular vitreous strands and veils

Mild or occasionally moderate to severe myopia

Presenile cataract

Night blindness of variable degree associated with progressive chorioretinal atrophy

Retinal detachment at advanced stages of the disease

Reduced visual acuity resulting from the above manifestations

Absence of systemic abnormalities

The clinical diagnosis of VCAN-related vitreoretinopathy is established based on typical clinical findings and a family history consistent with autosomal dominant inheritance. The presence of several affected family members facilitates diagnosis by identifying the mode of inheritance and spectrum of ocular findings among affected family members at different ages. In general, it is the pattern of ocular findings in an individual or a family rather than a specific ocular finding that helps establish the diagnosis. Establishing the diagnosis may be more difficult in a simplex case (i.e., a single occurrence in a family).

Molecular Genetic Testing

Gene. VCAN (previously CSPG2), encoding the large extracellular matrix proteoglycan versican, is the only gene currently known to be associated with Wagner syndrome and erosive vitreoretinopathy (ERVR) .

Clinical testing

Sequence analysis. Sequence analysis of the entire VCAN coding region and flanking introns performed

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