Title: Stickler Syndrome
Author (s): Michael R. Christensen, MS-IV, Virginia Commonwealth University School of Medicine; Charles Calvo, MD.
Photographer: Moran Eye Center Photography
Keywords/Main Subjects: Stickler Syndrome
Diagnosis: Stickler Syndrome
Secondary CORE Categories: Retina and Vitreous / Congenital and Developmental Abnormalities
Brief Description: The Stickler Syndromes, also known as hereditary or progressive oculoarthropathy, refer to a collection of chromosomal mutations most commonly inherited in an autosomal dominant pattern associated with abnormal collagen production (types II, IX, and XI) all of which are components of vitreous. The condition often manifests early in life with primarily ocular symptoms but may include other systemic symptoms.
Age & Gender: The condition classically presents in the pediatric population in the setting of other facial and systemic findings. It can also be detected after retinal detachment at any age, but most commonly in young adulthood. It does not have a strong gender preference.
Genotype: Several genetic loci have been implicated in this disease. The most common autosomal dominant form is associated with mutations in a large gene on chromosome 12, encoding type II collagen (Type 1, COL2A1). Less common forms include defects in genes on chromosome 1, encoding type XI collagen (Type II, COL11A1) and chromosome 6 (type III, COL11A2). The rarest are autosomal recessive forms caused by defects in genes encoding type IX collagen (Type IV, COL9A1, COL9A2, COL9A3)
Symptoms: There is a wide range of symptoms depending on the underlying genetic defect. Type 1 and type 2 present similarly with ocular symptoms including visual field loss as result of rhegmatogenous retinal detachments, decreased visual acuity secondary to myopia or cataract, and elevated intraocular pressure due to associated juvenile-onset open angle glaucoma. Classic systemic symptoms include hearing loss and joint pain. The syndrome may present with micrognathia and macroglossia resulting in cleft palate (Pierre-Robin sequence). Type 2 is characterized by the exam finding of beaded vitreous. Type 3 has systemic symptoms but lacks ocular involvement. Type 4 has ocular involvement but lacks systemic findings.
Environmental Factors or Other Considerations: The only known risk factor is a family history of the condition. A child of an affected parent has at least a 50% chance of manifesting the condition. Retinal detachment is estimated to occur in 65% of affected patients.
Treatment: There is no treatment of Stickler syndrome for the underlying genetic deficiency, so treatments are aimed at managing the complications. There is growing evidence to suggest that 360-degree cryotherapy or laser may reduce rates of retinal detachment, but studies have been based on retrospective analyses. Cataracts can be removed surgically, which may improve acuity, but the decision to perform cataract surgery must be carefully considered because of the increased risk of retinal detachment in Stickler syndrome and after cataract surgery. Glaucoma may be treated medically and surgically.
Pathophysiology: Collagen is an important component of human vitreous. Normal collagen is composed of three fibrils formed from polypeptide chains that are processed into stable trimers. Mutations in collagen genes lead to dysfunction of the production and assembly of the polypeptide chains, resulting in unstable mature collagen and the clinical manifestations of Stickler Syndrome.
Differential Diagnosis: Knobloch syndrome, Wagner syndrome, Multiple Epiphyseal dysplasia, Metatropic dysplasia, Marshall Syndrome
- Originally published in: Hartnett, Mary Elizabeth. Pediatric retina: medical and surgical approaches. 2nd Ed. Philadelphia: Lippincott Williams & Wilkins, 2005.
- 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 Feb;132(2):368-71. PubMed PMID: 9506662.
- Annunen S, Körkkö J, Czarny M, Warman ML, Brunner HG, Kääriäinen H, Mulliken JB, Tranebjaerg L, Brooks DG, Cox GF, Cruysberg JR, Curtis MA, Davenport SL, Friedrich CA, Kaitila I, Krawczynski MR, Latos-Bielenska A, Mukai S, Olsen BR, Shinno N, Somer M, Vikkula M, Zlotogora J, Prockop DJ, Ala-Kokko L. Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes.Am J Hum Genet. 1999 Oct;65(4):974-83. PubMed PMID: 10486316; PubMed Central PMCID: PMC1288268.
- Hromas, Alan. American Academy of Ophthalmology. Eye Wiki: Stickler Syndrome. 2017
- Wubben TJ,Branham KH, Besirli CG, Bohnsack BL. Retinal detachment and infantile-onset glaucoma in Stickler syndrome associated with known and novel COL2A1 mutations. Ophthalmic Genet. 2018 Aug 21:1-4.
Faculty Approval by: M. E. Hartnett, MD
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