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Stickler syndrome: for professionals


Incidence1 in 7,500
InheritanceAutosomal dominant and autosomal recessive
Genes involved (OMIM No.)COL2A1 (#120140), COL11A1 (#120280), COL11A2 (#120290), COL9A1 (#120210), COL9A2 (#120260), COL9A3 (#120270)
SymptomsReduced vision (types 1, 2 and 4)
Hearing loss
Joint pain
Ocular FeaturesMyopia Vitreous abnormalities
Retinal detachment
Cataracts Glaucoma
Systemic FeaturesSensorineural hearing loss
Conductive hearing loss (from recurrent ear infections/glue ear)
Joint hypermobility
Early-onset arthritis
Craniofacial abnormalities
Key InvestigationsUltra-wide field imaging (Optos)
Optical coherence tomography
Fundus autofluorescence
Ultrasound biomicroscopy
Gonioscopy and tonometry
Skeletal imaging (x-rays)
Genetic TestingTargeted sequencing of specific
Stickler-associated genes (R45 panel)
ManagementOcular Prophylactic retinopexy if indicated
Retinal detachment repair surgery
Regular ophthalmic follow-up
Systemic Paediatric/clinical genetics review
Multidisciplinary approach if systemic features are present
Therapies under ResearchNatural history studies
Prevention of retinal detachment studies

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Clinical phenotype

Stickler syndrome is a connective tissue disorder that can present with ocular findings such as myopia, cataract and retinal detachment. It is the most common cause of rhegmatogenous retinal detachment in childhood. It can also present with systemic manifestations including craniofacial underdevelopment and hearing loss. There is variable expression of the phenotype depending on the subtype of Stickler syndrome and whether is it autosomal dominant or recessive.1

Presenting features

Stickler Syndrome Type I:

  1. Genetics: COL2A1 (autosomal dominant)
  2. Phenotype:
    • Ocular features: high myopia detectable in neonates and is progressive, membranous vitreous (involves a folded membrane bordering vestigial vitreous gel)2, spontaneous retinal detachment, cataracts, glaucoma.3,4
    • Auditory features: sensorineural hearing loss or conductive hearing loss (due to recurrent infections associated with cleft palate). This is usually mild and not progressive.5
    • Systemic features: early-onset arthritis, craniofacial abnormalities (such as cleft palate, mid-facial hypoplasia, or airway abnormalities), Pierre Robin Sequence.6
    • Most common form, affecting 80-90% of patients.1

Stickler Syndrome Type II:

  1. Genetics: COL11A1 (autosomal dominant)7
  2. Phenotype:
    • Ocular features: Fibrillar or beaded vitreous, otherwise similar to type 1 but generally less severe.
    • Systemic features: similar to type 1, but more severe midface hypoplasia and sensorineural hearing loss.

Stickler Syndrome Type III:

  1. Genetics: COL11A2 (autosomal dominant)8,9
  2. Phenotype:
    • No ocular involvement
    • Systemic features: similar to type 1.

Stickler Syndrome Type IV:

  1. Genetics: COL9A1 and COL9A2, COL9A3 (autosomal recessive)10
  2. Phenotype:
    • Ocular features: moderate to high myopia with vitreoretinopathy, less frequent retinal detachments.
    • Almost all individuals are affected by sensorineural hearing loss (moderate to severe). No cleft palate has been reported in this group.

Non-classic Stickler Syndrome:

  1. Some individuals with Stickler-like features do not fit precisely into the established types.
  2. May involve a combination of ocular, auditory, and skeletal abnormalities.
  3. Genetic basis may not be identified or could involve other genes.1

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Stickler syndrome caused by pathogenic variants in COL2A1COL11A1, or COL11A2 is inherited in an autosomal dominant manner and Stickler syndrome caused by pathogenic variants in COL9A1COL9A2, or COL9A3 is inherited in an autosomal recessive manner. The genes are involved in normal production and function of collagen types II, IX and XI.1,11

The following are the main genes involved.

  1. COL2A1 (OMIM: #120140):
    • Function: COL2A1 encodes the alpha-1 chain of type II collagen, a vital structural protein in cartilage, vitreous humour, and other connective tissues. Type II collagen provides essential support and integrity to these tissues.
    • Effect: Mutations in COL2A1 disrupt the formation of normal collagen fibrils, leading to structural abnormalities in cartilage and the vitreous humour. This disruption results in the characteristic skeletal deformities, joint hypermobility, and ocular manifestations observed in Stickler syndrome patients.
  2. COL11A1 (OMIM: #120280):
    • Function: COL11A1 codes for the alpha-1 chain of type XI collagen, a fibrillar collagen crucial for the development of cartilage and vitreous humour.
    • Effect: Pathogenic variants in COL11A1 disturb the normal assembly of collagen fibrils, impacting cartilage integrity and vitreous structure.
  3. COL11A2 (OMIM: #120290):
    • Function: COL11A2 encodes the alpha-2 chain of type XI collagen, also present in cartilage and the vitreous humour.
    • Effect: Mutations in COL11A2 lead to abnormalities in collagen fibril formation, affecting cartilage and vitreous humour structure. Consequently, patients exhibit symptoms such as joint hypermobility and vitreoretinal degeneration.
  4. COL9A1 (OMIM: #120210), COL9A2 (OMIM: #120260), COL9A3 (#120270):
    • Function: These genes encode the alpha chains of type IX collagen, contributing to cartilage integrity.
    • Effect: Disruption results in skeletal abnormalities, joint laxity, and other clinical features of Stickler syndrome.

Further information about each gene can be found on OMIM and Medline Plus.

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Key investigations


  1. Slit lamp examination:
    • Classically, Stickler vitreous is described as “optically empty”. Membranous vitreous appears as a collection of gel in the immediate retrolental space, posteriorly bounded by a membranous condensation. The beaded vitreous contains diffuse, sparse lamellae with a beaded appearance.12
  2. Fundoscopy:
    • Visualisation of any retinal tears or detachments.1
  3. Ultra-wide field imaging (Optos):
    • Visualisation of the peripheral retina to assess for tears or detachment.
  4. Visual acuity:
    • High myopia greater than -3 dioptres.
  5. Fundus auto-fluorescence:
    • It is used the health of the retina.
  6. Optical Coherence Tomography (OCT):
    • It can assess if the macula is on or off in retinal detachments, which can aid with triage decisions.
  7. Ultrasound B-scan:
    • It measures the axial length as patients are typically myopic.
  8. Intraocular pressure:
    • To assess for glaucoma
  9. Genetic testing:
    • Stickler panel (R45) if high suspicion.


  1. Audiological assessment:
    o To assess for sensorineural and conductive hearing loss
  2. Clinical, Radiographic, and Orthopaedic Assessments:
    o To assess for craniofacial underdevelopment and early onset arthritis.

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The diagnosis is primarily achieved through genetic testing, identifying pathogenic variants in COL2A1, COL11A1, COL11A2, COL9A1, or COL9A2.

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Differential Diagnosis

Apart from Stickler Syndrome, similar presentations can be observed in conditions like Pierre Robin Sequence, Binder Syndrome, and certain high-grade myopia disorders.13

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  1. Regular ophthalmology assessment:
    • To correct refractive errors and assess for retinal tears.
  2. Vitreoretinal surgery:
    • Stickler syndrome patients often develop spontaneous giant retinal tears which often respond poorly to traditional retinal detachment surgery compared to non-stickler detachments. Therefore, high risk patients may be offered prophylactic retinopexy or cryopexy. This depends on each individual presentation and the protocols of the Stickler Clinic. Patients who present with retinal detachment should have surgery to repair this.14-17
  3. Education:
    •  Patients should be educated about the risks and symptoms of retinal detachment to enable early intervention if this occurs. Patients should also be advised to wear eye protection during contact sports.


  1. Hearing impairment (referral to audiology):
    • Hearing aids: Utilised as necessary to address varying degrees of hearing loss.
    • Otitis Media Management: Prompt treatment and consideration of myringotomy tubes for recurrent cases.
  2. Craniofacial (referral to Maxillofacial):
    • Mandibular advancement procedures: Address persistent micrognathia and correct malocclusion.
    • Cleft palate management: Led by craniofacial specialists, including feeding and nutritional support.
  3. Arthritis (referral to Rheumatology/Orthopaedics):
    • Symptomatic treatment: Involving over-the-counter anti-inflammatory medications and physical therapy.
    • Surgical interventions: Joint replacements in severe cases of osteoarthrosis.

Family management and counselling

Patients and families require genetic counselling and can seek advice for family planning including prenatal testing and preimplantation genetic diagnosis.

Emotional and social support

Eye Clinic Liaison Officers (ECLOs) act as an initial point of contact for newly diagnosed patients and their parents in clinic. They provide emotional and practical support to help patients and parents deal with the diagnosis and maintain independence. They work closely with the local council’s sensory support team and are able to advise on the broad range of services provided, such as visual rehabilitation, home assessment, work and access to qualified teachers for children with visual impairment (QTVI) among other services.

Related links

Referral to a specialist centre

In the UK, patients should be referred to their local genomic ophthalmology (if available) or clinical genetics services to receive a more comprehensive genetic management of their conditions (genetic testing and genetic counselling) and having the opportunity to participate in clinical research. Patients should also be referred to the Cambridge Stickler Syndrome Highly Specialised Service where they can be evaluated for diagnosis and management.

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Current research

Research on Stickler Syndrome is currently focussed on understanding the genetic mechanisms and potential treatment options. An upcoming clinical trial will evaluate the effect of scleral buckling on prevention of retinal detachment (NCT04465188). Other trials focus on natural history studies (NCT00270686, NCT01793168).

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Further information and support

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  1. Mortier G. Stickler Syndrome. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024 [updated 2023 Sep 7; cited 2024 May 28]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1302/
  2. Parentin F, Sangalli A, Mottes M, Perissutti P. Stickler syndrome and vitreoretinal degeneration: correlation between locus mutation and vitreous phenotype. Apropos of a case. Graefes Arch Clin Exp Ophthalmol. 2001;239(4):316-9.
  3. Walters A, Lambert N, Bricel S, Hwang T, Ing E, Tehrani S. Case series of Stickler syndrome presenting with acute angle closure. J Glaucoma. 2020;29(11):992-4.
  4. Boysen KB, La Cour M, Kessel L. Ocular complications and prophylactic strategies in Stickler syndrome: a systematic literature review. Ophthalmic Genet. 2020;41(3):223-34.
  5. Acke FRE, De Leenheer EMR. Hearing loss in Stickler syndrome: an update. Genes (Basel). 2022;13(9):1571.
  6. Rose PS, Ahn NU, Levy HP, Ahn UM, Davis J, Liberfarb RM, et al. Thoracolumbar spinal abnormalities in Stickler syndrome. Spine (Phila Pa 1976). 2001;26(4):403-9.
  7. Majava M, Hoornaert KP, Bartholdi D, Bouma MC, Bouman K, Carrera M, et al. A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies. Am J Med Genet A. 2007;143A(3):258-64.
  8. Vikkula M, Mariman EC, Lui VC, Zhidkova NI, Tiller GE, Goldring MB, et al. Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus. Cell. 1995;80(3):431-7. doi: 10.1016/0092-8674(95)90493-x. PMID: 7859284.
  9. Sirko-Osadsa DA, Murray MA, Scott JA, Lavery MA, Warman ML, Robin NH. Stickler syndrome without eye involvement is caused by mutations in COL11A2, the gene encoding the alpha2(XI) chain of type XI collagen. J Pediatr. 1998;132(2):368-71.
  10. Nixon TRW, Richards AJ, Martin H, Alexander P, Snead MP. Autosomal recessive Stickler syndrome. Genes (Basel). 2022;13(6):1135.
  11. Donoso LA, Edwards AO, Frost AT, Ritter R 3rd, Ahmad N, Vrabec T, et al. Clinical variability of Stickler syndrome: role of exon 2 of the collagen COL2A1 gene. Surv Ophthalmol. 2003;48(2):191-203.
  1. Parma ES, Korkko J, Hagler WS, Ala-Kokko L. Radial perivascular retinal degeneration: a key to the clinical diagnosis of an ocular variant of Stickler syndrome with minimal or no systemic manifestations. Am J Ophthalmol. 2002;134(5):728-34.
  2. Karempelis P, Hagen M, Morrell N, Roby BB. Associated syndromes in patients with Pierre Robin sequence. Int J Pediatr Otorhinolaryngol. 2020;131:109842.
  3. Morris RE, Parma ES, Robin NH, Sapp MR, Oltmanns MH, West MR, et al. Stickler syndrome (SS): laser prophylaxis for retinal detachment (modified ora secunda cerclage, OSC/SS). Clin Ophthalmol. 2021;15:19-29.
  4. Alexander P, Snead MP. Prevention of blindness in Stickler syndrome. Genes (Basel). 2022;13(7):1150.
  5. Lee AC, Greaves GH, Rosenblatt BJ, Deramo VA, Shakin EP, Fastenberg DM, et al. Long-term follow-up of retinal detachment repair in patients with Stickler syndrome. Ophthalmic Surg Lasers Imaging Retina. 2020;51(10):612-6.
  6. Khanna S, Rodriguez SH, Blair MA, Wroblewski K, Shapiro MJ, Blair MP. Laser prophylaxis in patients with Stickler syndrome. Ophthalmol Retina. 2022;6(3):263-7.

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Updated on June 2, 2024
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