Radial perivacular retinal degeneration: a key to the clinical diagnoi of an ocular variant of tickler yndrome with minimal or no ytemic manifetation

PURPOE: To identify the genetic defect and preent the ocular and extraocular finding in a large pedigree of predominantly ocular tickler yndrome. DEIGN: Obervational cae erie. METHOD: An eight-generation pedigree with hereditary retinal detachment wa retropectively and propectively tudied. Clinical information wa obtained by medical record, telephone interview, medical quetionnaire, detailed ophthalmologic examination, phyical examination, and peronal obervation. Linkage analyi of the COL2A1 gene wa performed on 21 family member, and mutation analyi wa performed on three family member. REULT: The pedigree conited of 100 affected individual. The ocular finding, frequently bilateral, conited of radial perivacular retinal degeneration (RPRD) (100%), vitreou ynerei (100%), high myopia (76%), retinal detachment (65%), preenile cataract development (occurring before 50 year of age; 78%), and glaucoma (18%). Mot (70%) of the retinal detachment occurred between 4 and 18 year of age. Extraocular manifetation, characteritic for tickler yndrome, were detected in only four of 100 (4%) affected individual. Linkage analyi with COL2A1 flanking marker howed evidence for linkage to the COL2A1 locu. The COL2A1 gene analyi identified a mutation converting a codon TGC for cyteine86 to a premature termination codon in the alternatively pliced exon 2. CONCLUION: A variant of tickler yndrome, caued by mutation in exon 2 of COL2A1, may preent in familie with all of the ocular finding and no clinically identifiable extraocular finding aociated with tickler yndrome. The predominant ocular finding are a congenitally abnormal vitreou and an acquired radial perivacular retinal degeneration that may lead to complicated childhood and adult retinal detachment.