STICKLER SYNDROME - CORRELATION BETWEEN VITREORETINAL PHENOTYPES AND LINKAGE TO COL 2A1

Stickler syndrome is an autosomal dominantly inherited condition chara cterised by ocular, articular, facial, auditory and oral features. The re is locus heterogeneity with about two thirds of families showing li nkage to the gene encoding type II procollagen (COL 2A1), Clinical ove rlap with Marshall's, Wagner's and other syndromes has caused consider able confusion but the importance of the congenital vitreous anomaly, as first described by Scott, has not previously been emphasised. This study examines the linkage of two vitreo-retinal phenotype subgroups o f Stickler syndrome to COL 2A1. A total of 97 affected patients from 2 4 pedigrees were examined. This is the largest published series of Sti ckler syndrome patients to date and all have undergone full clinical a nd ophthalmological examination by a single investigator, A clinical c lassification is proposed based on vitreoretinal phenotype, All patien ts demonstrating the congenital vitreous anomaly have been designated Stickler syndrome type 1 and those without the congenital vitreous ano maly as Stickler syndrome type 2 patients, There were 69 affected pati ents from 20 unrelated type 1 pedigrees and 28 affected patients from 4 unrelated type 2 pedigrees, Using two markers at the COL 2A1 locus, Stickler syndrome type 1 pedigrees showed complete linkage to COL 2A1 with a maximum lod score of 12.33 at zero recombination, Linkage to CO L 2A1 was excluded in the two type 2 pedigrees that were informative, From these data it appears that this clinical classification is a usef ul first step in resolving the genetic heterogeneity in this condition .