Dominant Stickler Syndrome

Abstract

The Stickler syndromes are a group of genetic connective tissue disorders associated with an increased risk of rhegmatogenous retinal detachment, deafness, cleft palate, and premature arthritis. This review article focuses on the molecular genetics of the autosomal dominant forms of the disease. Pathogenic variants in COL2A1 causing Stickler syndrome usually result in haploinsufficiency of the protein, whereas pathogenic variants of type XI collagen more usually exert dominant negative effects. The severity of the disease phenotype is thus dependent on the location and nature of the mutation, as well as the normal developmental role of the respective protein.

Keywords: COL11A1; COL2A1; Stickler syndrome; giant retinal tear; retinal detachment; vitreous.

Figure 1

Schematic illustrations of vitreous phenotypes associated with Stickler syndrome. (a) Membranous congenital vitreous anomaly, (b) Beaded congenital vitreous anomaly. Reproduced with permission from Snead et al. [13].

Figure 2

Locations of pathogenic variants associated with each syndrome. Genes associated with AD Stickler syndrome are in red, and genes associated with the differential diagnoses are in green.

Figure 3

Structural relationship between types II, IX, and XI collagen.

Figure 4

(Top) 210 degrees Giant Retinal Tear identified in an otherwise asymptomatic 8-year-old child with type 1 Stickler syndrome. (Bottom) Giant Retinal Tear in child with undiagnosed type 1 Stickler syndrome. Reproduced with permission from Snead et al. [13].