Radial perivascular retinal degeneration: a key to the clinical diagnosis of an ocular variant of Stickler syndrome with minimal or no systemic manifestations.
OBJECTIVE
To identify the genetic defect and present the ocular and extraocular findings in a large pedigree of predominantly ocular Stickler syndrome.


METHODS
Observational case series.


METHODS
An eight-generation pedigree with hereditary retinal detachments was retrospectively and prospectively studied. Clinical information was obtained by medical records, telephone interviews, medical questionnaires, detailed ophthalmologic examinations, physical examinations, and personal observations. Linkage analysis of the COL2A1 gene was performed on 21 family members, and mutation analysis was performed on three family members.


RESULTS
The pedigree consisted of 100 affected individuals. The ocular findings, frequently bilateral, consisted of radial perivascular retinal degeneration (RPRD) (100%), vitreous syneresis (100%), high myopia (76%), retinal detachment (65%), presenile cataract development (occurring before 50 years of age; 78%), and glaucoma (18%). Most (70%) of the retinal detachments occurred between 4 and 18 years of age. Extraocular manifestations, characteristic for Stickler syndrome, were detected in only four of 100 (4%) affected individuals. Linkage analysis with COL2A1 flanking markers showed evidence for linkage to the COL2A1 locus. The COL2A1 gene analysis identified a mutation converting a codon TGC for cysteine(86) to a premature termination codon in the alternatively spliced exon 2.


CONCLUSIONS
A variant of Stickler syndrome, caused by mutations in exon 2 of COL2A1, may present in families with all of the ocular findings and no clinically identifiable extraocular findings associated with Stickler syndrome. The predominant ocular findings are a congenitally abnormal vitreous and an acquired radial perivascular retinal degeneration that may lead to complicated childhood and adult retinal detachment.
Parma
Edward S
ES
Retina Specialists of Alabama LLC, Birmingham, Alabama 35205, USA. e63parm@aol.com
Körkkö
Jarmo
J
Hagler
William S
WS
Ala-Kokko
Leena
L
D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator / Q000235:genetics*; D024043:Collagen Type II / Q000235:genetics*; D003240:Connective Tissue Diseases / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D012163:Retinal Detachment / Q000175:diagnosis / Q000235:genetics; D012171:Retinal Vessels / Q000473:pathology; D012189:Retrospective Studies; D013577:Syndrome
C499177:COL2A1 protein, human; D018388:Codon, Terminator; D024043:Collagen Type II