Retinal detachment in Type IX collagen recessive Stickler syndrome.

Objective: Stickler Syndrome (SS) is associated with eye, joint and orofacial abnormalities. Most cases are dominantly inherited through COL2A1/COL11A1 variants encoding type-II/XI collagen, with patients having up to 78% retinal detachment (RD) risk. Rarer cases of recessive SS have also been identified, associated with pathogenic variants of genes including COL9A1, COL9A2 & COL9A3 encoding type-IX collagen, but there is limited published data on patients' phenotype or RD risk.

Peripapillary Hyperreflective Ovoid Mass-Like Structures in Stickler Syndrome.

Purpose: To report a previously undescribed finding of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in Stickler syndrome.

Design: Noncomparative case series.

Subjects: Twenty-two eyes with anomalous optic disc from 11 Stickler syndrome patients were identified and imaged.

Retinal detachment risk in the fellow eyes of patients presenting with retinal tears in more than two quadrants.

Literature discussing fellow eye risk in patients with rhegmatogenous retinal detachment secondary to posterior vitreous detachment (PVD) is limited, particularly in subgroups where this risk may be greater than the general population. In this retrospective consecutive case series with 107 study patients, the risk of retinal tears in fellow eyes of patients with horseshoe tears in three or more quadrants of their presenting eye, secondary to PVD, was 81%. The fellow eye risk is high in this subgroup of patients, and it is important to inform them to seek prompt attention when symptoms of PVD develop in their fellow eye.

Posterior Vitreous Detachment and the Posterior Hyaloid Membrane.

Purpose: Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise anatomic definition. We investigated the morphologic appearance and molecular composition of the posterior hyaloid membrane to determine whether the structure clinically observed enveloping the posterior vitreous surface after posterior vitreous detachment is a true basement membrane and to postulate its origin. Understanding the relationship between the vitreous (in both its attached and detached state) and the internal limiting membrane of the retina is essential to understanding the cause of rhegmatogenous retinal detachment and vitreoretinal interface disorders, as well as potential future prophylactic and treatment strategies.

Deep Intronic Sequence Variants in COL2A1 Affect the Alternative Splicing Efficiency of Exon 2, and May Confer a Risk for Rhegmatogenous Retinal Detachment.

COL2A1 mutations causing haploinsufficiency of type II collagen cause type 1 Stickler syndrome that has a high risk of retinal detachment and failure of the vitreous to develop normally. Exon 2 of COL2A1 is alternatively spliced, expressed in the eye but not in mature cartilage and encodes a region that binds growth factors TGFβ1 and BMP-2. We investigated how both an apparently de novo variant and a polymorphism in intron 2 altered the efficiency of COL2A1 exon 2 splicing and how the latter may act as a predisposing risk factor for the occurrence of posterior vitreous detachment (PVD)-associated rhegmatogenous retinal detachment (RRD) in the general population.

Prevention of retinal detachment in Stickler syndrome: the Cambridge prophylactic cryotherapy protocol.

Purpose: The Stickler syndromes are the most common causes of inherited and childhood retinal detachment; however, no consensus exists regarding the effectiveness of prophylactic intervention. We evaluate the long-term safety and efficacy of the Cambridge prophylactic cryotherapy protocol, a standardized retinal prophylactic treatment developed to prevent retinal detachment arising from giant retinal tears in type 1 Stickler syndrome.

Design: Retrospective comparative case series.

Alternative splicing modifies the effect of mutations in COL11A1 and results in recessive type 2 Stickler syndrome with profound hearing loss.

Background: Stickler syndromes types 1, 2 and 3 are usually dominant disorders caused by mutations in the genes COL2A1, COL11A1 and COL11A2 that encode the fibrillar collagens types II and XI present in cartilage and vitreous. Rare recessive forms of Stickler syndrome exist that are due to mutations in genes encoding type IX collagen (COL9A1 type 4 Stickler syndrome and COL9A2 type 5 Stickler syndrome). Recently, recessive mutations in the COL11A1 gene have been demonstrated to result in fibrochondrogenesis, a much more severe skeletal dysplasia, which is often lethal.

Retinal detachment and prophylaxis in type 1 Stickler syndrome.

Purpose: To report the prevalence of retinal detachment (RD) and results of prophylaxis against detachment from a giant retinal tear in a large cohort of patients with type 1 Stickler syndrome.

Design: Retrospective study.

Participants: Two hundred four type 1 Stickler syndrome patients.

Missense and silent mutations in COL2A1 result in Stickler syndrome but via different molecular mechanisms.

Stickler syndrome due to mutations in COL2A1 is usually the result of premature termination codons and nonsense mediated decay resulting in haploinsufficiency of type II collagen. Here we present two missense mutations and one apparently silent mutation that each result in Stickler syndrome, but via different molecular mechanisms. One alters the translation initiating ATG codon.

Clinical characterisation and molecular analysis of Wagner syndrome.

Aim: To detail the clinical findings in a British family with molecularly characterised Wagner syndrome.

Background: Only in the last year has the specific genetic defect in Wagner syndrome been identified, and the background literature of the molecular genetics is outlined. Clinical and laboratory findings in a second case of Wagner syndrome are included to highlight difficulties that can be encountered when identifying pathogenic mutations for disorders arising in complex genes.