ONLINE MUTATION REPORT Clinical features of type 2 Stickler syndrome

T he Stickler syndromes (hereditary arthro-ophthalmopathy; McKusick nos. 108300 and 604841) are one of the more frequently occurring groups of chondrodysplasias and are the commonest inherited cause of rhegmatogenous retinal detachment. The majority of patients and pedigrees exhibit the type 1 or ‘‘membranous’’ vitreous phenotype 11 and harbour mutations in the gene for type II collagen (COL2A1). While not all mutations in type II collagen result in the membranous vitreous anomaly, 23 when it is exhibited it appears to be congenital and provides a useful basis for mutant locus assignment. This is particularly helpful for sporadic cases where linkage is impossible, and especially in those individuals with mild or minimal systemic involvement where the diagnosis might otherwise be overlooked. 24–26 Other pedigrees exhibit a different ‘‘beaded’’ vitreous phenotype and are linked to a different locus. 27 We reported the first mutation in the gene encoding the a1 chain of type XI collagen (COL11A1) in one of these pedigrees and this locus was confirmed in other pedigrees, 30 and is now known as type 2 Stickler syndrome (McKusick no. 604841). The intimate post-translational molecular associations between types II and XI collagen form the foundation of the close clinical overlap between these two sub-groups of Stickler syndrome, but the extent of this clinical overlap and variation remains to be defined. Whilst type 1 Stickler syndrome pedigrees have a particularly high risk of blindness through giant retinal tear and retinal detachment, Annunen et al suggest that patients with COL11A1 mutations are at a low risk of retinal detachment and have a higher incidence of midfacial hypoplasia. This would be an important prognostic difference if confirmed. Here we wish to report the first description of the ophthalmic, oro-facial, audiologial, skeletal, and echocardiographic features of a large cohort of patients with type 2 Stickler syndrome in which molecular genetic analysis has confirmed mutations in COL11A1.