What is Stickler syndrome?

From the Guidelines

Stickler syndrome is a genetic disorder that affects connective tissue throughout the body, primarily impacting the eyes, ears, joints, and facial features, and is caused by mutations in several genes, most commonly COL2A1, as noted in the study by 1. The syndrome is characterized by a range of ocular features, including high myopia, retrolental, transvitreal, and epiretinal membranes and strands, chorioretinal pigment alterations, lattice degeneration, and various other abnormalities such as glaucoma and cataract, as described in the study by 1. Systemic features of Stickler syndrome include a generalized skeletal dysplasia, often with a marfanoid habitus, flattened facies, high arched or cleft palate, hearing loss, and other extracranial skeletal anomalies, many of which can be very subtle, as reported in the study by 1. Some key points about Stickler syndrome include:

• It is the most common inherited vitreoretinal and systemic disorder associated with retinal detachment, as noted in the study by 1
• The inheritance pattern is autosomal dominant, and a gene defect has been related to COL2A1, as described in the study by 1
• Eye problems are common and can include severe nearsightedness, cataracts, glaucoma, and retinal detachment, which may lead to vision loss, as reported in the study by 1
• Hearing loss, both conductive and sensorineural, affects many patients, and joint problems resembling early-onset arthritis, joint hypermobility, and skeletal abnormalities are also characteristic, as described in the study by 1 Treatment for Stickler syndrome focuses on managing specific symptoms through regular eye examinations, hearing assessments, orthopedic care, and sometimes surgical interventions for issues like cleft palate or retinal detachment, as noted in the study by 1.

From the Research

Definition and Characteristics of Stickler Syndrome

• Stickler syndrome is a connective tissue disorder characterized by ocular, skeletal, orofacial, and auditory manifestations 2.
• The main symptoms include high myopia, retinal detachment, joint hypermobility, early osteoarthritis, cleft palate, midfacial hypoplasia, micrognathia, and hearing loss 2.
• The syndrome is caused by genetic heterogeneity, including collagen genes (COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, COL9A3) and non-collagen genes (BMP4, LRP2, LOXL3) 2.

Ocular Manifestations

• Stickler syndrome is a systemic collagenopathy affecting multiple organ systems, including the eye, ear, and skeleton 3.
• It is probably the most common cause of genetically determined pediatric rhegmatogenous retinal detachment 3.
• Sixty percent of patients with Stickler syndrome develop rhegmatogenous retinal detachments over their lifetime, with possible severe visual loss and subsequent lifelong morbidity 3.

Hearing Loss

• Hearing loss is a common feature of Stickler syndrome, with the most frequent type (COL2A1) characterized by a rather mild high-frequency sensorineural hearing loss in about half of the patients 2.
• COL11A1- and COL11A2-related Stickler syndrome results in more frequent hearing loss, being moderate and involving all frequencies 2.

Genetic Basis

• The Stickler syndrome has been linked to the structural gene for type II collagen, with genetic linkage studies suggesting close linkage to the COL2A1 gene 4.
• The mutation causing Stickler syndrome affects the structural locus for type II collagen, at least in some families 4.

Prophylactic Treatment

• Prophylactic laser treatment to the retina of patients with Stickler syndrome may reduce the occurrence of and/or prevent future rhegmatogenous retinal detachment, but there is insufficient data to support the absolute benefit of such prophylactic treatment 3, 5.
• A systematic review found that 360° cryotherapy and focal or circumferential laser treatment may be effective in preventing retinal detachment in patients with Stickler syndrome, but the evidence is uncertain due to a high risk of bias 5.
• Recent studies have reported successful prevention of rhegmatogenous retinal detachment in Stickler syndrome using 360-degree (encircling) laser retinopexy, providing strong evidence for similar prophylaxis in non-syndromic eyes at high risk of retinal detachment 6.