Clinical and molecular genetics of Stickler syndrome

Abstract

Stickler syndrome is an autosomal dominant disorder with characteristic ophthalmological and orofacial features, deafness, and arthritis. Abnormalities of vitreous gel architecture are a pathognomonic feature, usually associated with high myopia which is congenital and non-progressive. There is a substantial risk of retinal detachment. Less common ophthalmological features include paravascular pigmented lattice degeneration and cataracts. Non-ocular features show great variation in expression. Children with Stickler syndrome typically have a flat midface with depressed nasal bridge, short nose, anteverted nares, and micrognathia. These features can become less pronounced 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 radiologically. Sensorineural deafness with high tone loss may be asymptomatic or mild. Occasional findings include slender extremities and long fingers. Stature 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 show the characteristic type 1 vitreous phenotype. The remainder with the type 2 vitreous phenotype have mutations in COL11A1 or other loci yet to be identified. Mutations in COL111A2 can give rise to a syndrome with the systemic features of Stickler syndrome but no ophthalmological abnormality.