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Stickler Syndrome

Stickler's Syndrome

Stickler syndrome, or arthro-ophthalmopathy, is a genetic disorder affecting the connective tissues, with patients presenting with ocular abnormalities, hearing loss, facial malformations and skeletal problems.


Owing to the multi-system nature of the disease, people with Stickler syndrome present with a variety of clinical features, the most common amongst them being ophthalmological abnormalities, hearing deficits, a distinctive facial appearance and multiple musculo-skeletal defects.

A frequent eye finding seen in Stickler syndrome is vitreoretinal degeneration, that causes floaters to appear in an individual's field of vision [1]. Patients thus, become more prone for partial/ complete retinal detachment, that may manifest as flashes, floaters or sudden blindness. Cataracts, astigmatism and strabismus also contribute to the decrease in visual acuity. Glaucomatous changes have been observed in 5-10% of affected individuals.

Auditory deficits are commonly observed in Stickler syndrome. The hearing loss may be either conductive or sensorineural or mixed in nature [2]. It is often more severe and progressive in type II Stickler syndrome. Other otologic problems include chronic otitis media, glue ear and increased mobility of the bones of the middle ear.

Affected patients may also suffer from a multitude of cranio-facial abnormalities, with the face appearing flattened due to a small and flat nose, long philtrum, large eyes and hypoplastic bones. Some may present with the Pierre-Robin sequence, a group of cranial malformations comprising of a cleft palate, glossoptosis, micrognathia and a bifid uvula. Children may have difficulties in breathing and feeding due to these defects. Malocclusion of the upper/ lower teeth is also seen in a few individuals.

Amongst the musculoskeletal complaints usually seen, painful, stiff joints with early osteoarthritis is a common finding. Abnormally lax joints leading to dislocations are seen early in the course of the disease. Other frequent findings include: spinal deformities such as kyphosis, scoliosis, spondylolisthesis [3]; chest malformations in the form of pectus carinatum and excavatum; and limb anomalies such as arachnodactyly, pes planus, hypotonia and Legg-Calve-Perthes disease.

Learning disabilities and mitral valve prolapse have also been observed in a few individuals [4].

  • Audiologists and speech-language pathologists should be familiar with the characteristics associated with Stickler syndrome to facilitate early identification and appropriate management.[ncbi.nlm.nih.gov]
  • […] are likely to be involved in the treatment of those with Stickler's syndrome, include anesthesiologists, oral and maxillofacial surgeons ; craniofacial surgeons; ear, nose, and throat specialists, ophthalmologists, optometrists, audiologists, speech pathologists[en.wikipedia.org]
  • METHODS: Five patients of an Italian family affected by high myopia, high frequency of retinal detachment, and other systemic stigmata evocative of Stickler syndrome (flat midface, depressed nasal bridge, short nose, spondyloepiphyseal dysplasia and osteoarthritis[ncbi.nlm.nih.gov]
  • Systemic findings may include micrognathia and macroglossia resulting in cleft palate (Pierre-Robin sequence: an unusually small mandible (micrognathia), posterior displacement or retraction of the tongue (glossoptosis), upper airway obstruction, and[eyewiki.aao.org]
  • Macroglossia and ankyloglossia are relatively rare findings, noted in 10-15% of reported cases. The combination of micrognathia and glossoptosis may cause severe respiratory and feeding difficulty in the newborn.[emedicine.medscape.com]
  • […] congenita Pseudo-Von Willebrand disease Mandibuloacral dysplasia with type B lipodystrophy Congenital muscular dystrophy type 1A Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation Dextrocardia Peters plus syndrome Macroglossia[checkrare.com]
Hearing Impairment
  • Stapedial fixation can be the cause of hearing impairment in Stickler syndrome type I (COL2A1). The hearing impairment can be improved by stapes surgery.[ncbi.nlm.nih.gov]
  • Severe myopia leading to blindness, cleft palate, or subnucous cleft, Pierre Robin anomaly, premature degenerative arthritis, or a family history of any of these indicates further evaluation.[ncbi.nlm.nih.gov]
Low Back Pain
  • Osteoarthritis (75% of patients) with onset before 30 years of age is a severe manifestation that causes chronic hip and low back pain and functional impairments. Joint replacement surgery is often required.[ncbi.nlm.nih.gov]
  • There are delays in diagnosis, lack of understanding among family members, denial about the risk of serious eye problems, and joint disease.[ncbi.nlm.nih.gov]


The diagnosis of Stickler syndrome is based on a combination of clinical findings, family history and genetic data. Diagnostic criteria, although proposed, have yet to reach a majority consensus [5].

Amongst the various clinical features, vitreo- retinal changes, sensorineural hearing loss and cleft palate are considered major manifestations (2 points each). Other auditory deficits and skeletal features make up the minor findings (1 point each). A diseased first-degree relative with autosomal dominant inheritance also aids in the diagnosis of Stickler syndrome. Criterion adding up to or greater than 5 points makes the individual more susceptible to this syndrome. The absence of an alternate diagnosis lends more weight to these findings.

The syndrome is however, confirmed by genetic studies demonstrating pathologic variants in the following six genes: COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, or COL9A3 [6] [7] [8] [9] [10]. Serial single or multi-gene panels may be used to evaluate the mutations present in such genes.


  • Individual patient matching protocols purposely weighted bias against the effectiveness of treatment. All treatment side effects are reported. MAIN OUTCOME MEASURES: Time to retinal detachment and side effects occurring after prophylactic treatment.[ncbi.nlm.nih.gov]
  • Tracheostomy may be needed in infants with Robin sequence; mandibular advancement can correct malocclusion for those with significant micrognathia; standard treatments for hearing loss and retinal detachment; and symptomatic treatment for arthropathy[preventiongenetics.com]


  • As PRS is aetiologically heterogeneous, the prognosis depends on the cause. Genetic investigations and familial history must be taken into account.[ncbi.nlm.nih.gov]
  • Prognosis There is currently no available data on long-term visual prognosis of Stickler syndrome; however, prophylactic treatment to prevent retinal detachment is expected to improve long term visual prognosis.[eyewiki.aao.org]


  • Use Additional Use Additional Help Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology.[icd10data.com]
  • Etiology Types 1-4 Stickler syndrome are classically inherited in an autosomal dominant fashion [3], though a significant number of cases may be sporadic. [2] Risk Factors The only known risk factor for Stickler syndrome is a family history of the condition[eyewiki.aao.org]
  • Etiology and Pathogenesis Frequency This heterogeneous birth defect has a prevalence of approximately 1 per 8500 live births. The male-to-female ratio is 1:1, except in the X-linked form. Etiology Autosomal recessive inheritance is possible.[emedicine.medscape.com]


  • Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate Craniofac J. 2004;41:47–52. Robin NH et al. Stickler Syndrome. GeneReviews 2000 June 9 (Updated 2014 Nov 26)[asperbio.com]
  • Epidemiology [ edit ] In the US, the estimated prevalence of Stickler syndrome is about 1 in 10,000 people, but it can affect as few as 1 in 100,000 in other areas of the world. [ citation needed ] History [ edit ] Scientists associated with the discovery[en.wikipedia.org]
  • Epidemiology of retinal detachment. ( 25817961 ) Vilaplana F....Mojal S. 2015 37 Giant premacular bursa: a novel finding of the posterior vitreous in two patients with Stickler syndrome type 1 revealed by swept-source optical coherence tomography. ( 26245341[malacards.org]
  • An inherited translocation defect has been identified in one Pierre Robin family. [ 3 ] Candidate genes and loci are under investigation. [ 4 ] Epidemiology Incidence PRS is a rare condition.[patient.info]
  • Epidemiology United States statistics The true incidence of LEMS is unknown. An estimated 3% of patients with SCLC have LEMS. The prevalence of SCLC is 5 cases per million population in the United States.[emedicine.medscape.com]
Sex distribution
Age distribution


  • This finding will have a major impact on the genetic counseling of patients with Stickler syndrome and on the understanding of the pathophysiology of collagens.[ncbi.nlm.nih.gov]
  • The pathophysiology of the spinal abnormalities in Stickler syndrome has not been fully defined.[medsci.org]
  • Pathophysiology Stickler syndrome is believed to be a direct result of abnormalities in the production of collagen types II, IX and XI, all of which are recognized as components of the human vitreous. [2] Normal collagen fibrils are composed of three[eyewiki.aao.org]
  • Pathophysiology Physiologic studies of neuromuscular transmission demonstrate that ACh release from the motor nerve terminal is impaired in the LEMS muscle.[emedicine.medscape.com]


  • Together with molecular data, ophthalmologists should consider genetic diagnosis of Stickler syndrome in patients with vitreous anomaly to prevent blindness from retinal detachment.[ncbi.nlm.nih.gov]
  • Prevention Stickler syndrome is an inherited condition and cannot be prevented. Genetic screening can help affected adults assess disease risk to their offspring. Early diagnosis and treatment is key to preventing serious complications.[innerbody.com]



  1. Vu CD, Brown J, Körkkö J, Ritter R, Edwards AO. Posterior chorioretinal atrophy and vitreous phenotype in a family with Stickler syndrome from a mutation in the COL2A1 gene. Ophthalmology. 2003;110(1):70-7.
  2. Snead MP, Yates JR. Clinical and Molecular genetics of Stickler syndrome. J Med Genet. 1999;36:353–9.
  3. Rose PS, Ahn NU, Levy HP, et al. Thoracolumbar spinal abnormalities in Stickler syndrome. Spine. 2001;26(4):403-9.
  4. Liberfarb RM, Goldblatt A. Prevalence of mitral-valve prolapse in the Stickler syndrome. Am J Med Genet. 1986;24(3):387-92.
  5. Rose PS, Levy HP, Liberfarb RM, et al. Stickler syndrome: clinical characteristics and diagnostic criteria. Am J Med Genet A. 2005;138A(3):199-207.
  6. Stickler GB, Belau PG, Farrell FJ, et al. Hereditary progressive arthro-ophthalmopathy. Mayo Clin Proc. 1965;40:433-55.
  7. 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.
  8. Van camp G, Snoeckx RL, Hilgert N, et al. A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet. 2006;79(3):449-57.
  9. Baker S, Booth C, Fillman C, et al. A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome. Am J Med Genet A. 2011;155A(7):1668-72.
  10. Faletra F, D'adamo AP, Bruno I, et al. Autosomal recessive Stickler syndrome due to a loss of function mutation in the COL9A3 gene. Am J Med Genet A. 2014;164A(1):42-7.

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Last updated: 2019-06-28 11:51