Stickler syndrome is an autosomal dominant disease caused by mutations in COL2A1, COL11A1 or COL11A2. The classic phenotype (STL1) is associated with mutations in COL2A1, a fibrillar collagen that is arrayed in quarter-staggered fashion to form fibers similar to those of COLI. Features of STL1 include progressive myopia, vitreoretinal degeneration, premature joint degeneration with abnormal epiphyseal development, midface hypoplasia, irregularities of the vertebral bodies, cleft palate deformity and variable sensorineural hearing loss (Ahmad et al., 1991; Ahmad et al., 1995; Brown et al., 1992). COLXI, a minor cartilage constituent, is also a fibrillar collagen. It is a trimer of three different polypeptides, alpha-1, alpha-2, and alpha-3, and is expressed in cartilaginous and non-cartilaginous tissues. STL2 is caused by mutations in COL11A1, and affected individuals have the characteristic ocular, auditory, and orofacial features of STL1 (
Richards et al., 1996
Sirko-Osadsa et al., 1998
). Mutations in COL11A2 cause STL3, a disease characterized by the typical facial features of STL1 in combination with hearing impairment. Cleft palate and mild arthropathy also occur, however ocular signs (high myopia, vitreoretinal degeneration, and retinal detachment) are absent (Vikkula et al., 1995). The phenotypic differences between STL3 and STL1/STL2 can be explained by the absence of COL11A2 in the vitreous, where it is replaced by COLV (Van Steensel et al., 1997).