Clinical and molecular genetics of Stickler syndrome

Stickler syndrome is an autosomal dominant disorder with characteristic oph thalmological and orofacial features, deafness, and arthritis. Abnormalitie s of vitreous gel architecture are a pathognomonic feature, usually associa ted with high myopia which is congenital and nonprogressive. There is a sub stantial risk of retinal detachment. Less common ophthalmological features include paravascular pigmented lattice degeneration and cataracts. Non-ocul ar features show great variation in expression. Children with Stickler synd rome typically have a fiat midface with depressed nasal bridge, short nose, anteverted nares, and micrognathia. These features can become less pronoun ced with age. Midline clefting, if present, ranges in severity from a cleft of the soft palate to Pierre-Robin sequence. There is joint hypermobility which declines with age. Osteoarthritis develops typically in the third or fourth decade. Mild spondyloepiphyseal dysplasia is often apparent radiolog ically. Sensorineural deafness with high tone loss may be asymptomatic or m ild. Occasional findings include slender extremities and long fingers. Stat ure and intellect are usually normal. Mitral valve prolapse was reported to be a common finding in one series but not in our experience. The majority of families with Stickler syndrome have mutations in the COL2A1 gene and sh ow the characteristic type 1 vitreous phenotype. The remainder with the typ e 2 vitreous phenotype have mutations in COL11A1 or other loci yet to be id entified. Mutations in COL11A2 can give rise to a syndrome with the systemi c features of Stickler syndrome but no ophthalmological abnormality.