title: Snowflake vitreoretinal degeneration: follow-up of the original family.
abstract: OBJECTIVE
  The ocular findings, systemic features, and genetic loci distinguishing known genetic causes of vitreoretinal degenerations were studied in the original Snowflake family.
  
  
  METHODS
  Prospective, comparative study and molecular genetic investigation.
  
  
  METHODS
  Members of the original snowflake vitreoretinal degeneration family.
  
  
  METHODS
  Clinical data were collected on 26 family members by history and examination. Thirteen of the 26 total family members underwent prospective examination. Linkage to known vitreoretinal degeneration loci (COL2A1, COL11A1, and the Wagner disease locus) was evaluated with short tandem repeat markers.
  
  
  METHODS
  Ocular and systemic features of known vitreoretinal degenerations.
  
  
  RESULTS
  Six of the 13 prospectively examined subjects had snowflake vitreoretinal degeneration. Corneal guttae (4/5; 80%), early onset cataract (5/6; 83%), fibrillar vitreous degeneration (6/6; 100%), and peripheral retinal abnormalities (5/6; 83%), including minute crystallinelike deposits called snowflakes (4/6; 67%), were common. Retinal detachment was seen in 1 of 6 of these prospectively examined subjects (17%). A total of 14 affected subjects were identified within the family, and in 3 (21%), retinal detachment developed. Orofacial features, early-onset hearing loss, and arthritis typical of Stickler syndrome were absent. Linkage to known vitreoretinal degeneration loci was excluded.
  
  
  CONCLUSIONS
  The absence of vitreous gel in the retrolental space and presence of fibrillar vitreous degeneration were consistent with the vitreous structure reported for collagen 11A1 (COL11A1) but not collagen 2A1 (COL2A1) mutations. The absence of systemic features was characteristic of the vitreoretinopathies linked to chromosome 5q13 (Wagner disease and erosive vitreoretinopathy) and mutations in exon 2 of the COL2A1 gene. Snowflakes in the peripheral retina and the absence of nyctalopia, posterior chorioretinal atrophy, and tractional retinal detachment were inconsistent with the chromosome 5q13 vitreoretinopathies. The association of Fuchs' corneal endothelial dystrophy found in this family has not been reported previously in other vitreoretinal degenerations. These findings and the exclusion of known genetic loci suggest snowflake is a distinct vitreoretinal degeneration.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Mike M
authors.initials: MM
authors.lastname: Lee
authors.forename: Robert
authors.initials: R
authors.lastname: Ritter
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hirose
authors.forename: Cuong D
authors.initials: CD
authors.lastname: Vu
authors.forename: Albert O
authors.initials: AO
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002386:Cataract / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D024161:Collagen Type XI / Q000235:genetics; D005128:Eye Diseases / Q000175:diagnosis* / Q000235:genetics; D015785:Eye Diseases, Hereditary / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005642:Fuchs' Endothelial Dystrophy / Q000175:diagnosis* / Q000235:genetics; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011446:Prospective Studies; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000235:genetics; D014822:Vitreous Body / Q000473:pathology*
chemical_list: D024161:Collagen Type XI