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Stickler syndrome

Reviewed January 2013

What is Stickler syndrome?

Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.

A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This is caused by underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features, called Pierre Robin sequence, is also common in people with Stickler syndrome. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.

Many people with Stickler syndrome have severe nearsightedness (high myopia). In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is visible upon eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities can cause impaired vision or blindness in some cases.

Another feature of Stickler syndrome is hearing loss. The degree of hearing loss varies among affected individuals and may become more severe over time.

Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) may also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.

Researchers have described several types of Stickler syndrome, which are distinguished by their genetic cause and their characteristic signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have hearing loss. Types IV and V are very rare and have only been diagnosed in a few individuals.

A similar condition called Marshall syndrome is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature, which is typically not seen in people with Stickler syndrome. Whether Marshall syndrome represents a variant of Stickler syndrome or a separate disorder is controversial.

How common is Stickler syndrome?

Stickler syndrome affects an estimated 1 in 7,500 to 9,000 newborns.

What genes are related to Stickler syndrome?

Mutations in the COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2 genes cause Stickler syndrome types I through V, respectively. Marshall syndrome, which may be a variant of Stickler syndrome, results from mutations in the COL11A1 gene.

The genes listed above are involved in the production of three types of collagen: type II, type IX, and type XI. Collagens are complex molecules that provide structure and strength to connective tissues that support the body's joints and organs. Type II, type IX, and type XI collagen are components of vitreous, cartilage, and other connective tissues.

Mutations in any one of these genes impair the production, processing, or assembly of type II, type IX, or type XI collagen. Defective collagen molecules or reduced amounts of collagen disrupt the development of connective tissues, leading to the characteristic features of Stickler syndrome.

Not all individuals with Stickler syndrome have mutations in one of the known genes. Researchers believe that mutations in other genes may also cause this condition, but those genes have not been identified.

Related Gene(s)

Changes in these genes are associated with Stickler syndrome.

  • COL11A1
  • COL11A2
  • COL2A1
  • COL9A1
  • COL9A2

How do people inherit Stickler syndrome?

Types I, II, and III Stickler syndrome (caused by mutations in the COL2A1, COL11A1, and COL11A2 genes) are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a gene mutation from one affected parent. Other cases may result from new mutations. These cases occur in people with no history of Stickler syndrome in their family.

Marshall syndrome also has an autosomal dominant pattern of inheritance.

Types IV and V Stickler syndrome (resulting from mutations in the COL9A1 or COL9A2 gene) are inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Stickler syndrome?

These resources address the diagnosis or management of Stickler syndrome and may include treatment providers.

  • Gene Review: Stickler Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1302)
  • Genetic Testing Registry: Marshall syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265235)
  • Genetic Testing Registry: Stickler syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265253)
  • Genetic Testing Registry: Stickler syndrome, type 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1858084)
  • Genetic Testing Registry: Stickler syndrome, type 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1861481)
  • Genetic Testing Registry: Stickler syndrome, type 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1852831)
  • Genetic Testing Registry: Stickler syndrome, type 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN116437)
  • Genetic Testing Registry: STICKLER SYNDROME, TYPE I, NONSYNDROMIC OCULAR (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1836080)
  • Genetic Testing Registry: Stickler syndrome type 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN032634)
  • MedlinePlus Encyclopedia: Pierre Robin syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001607.htm)
  • Merck Manual Home Health Handbook: Detachment of the Retina (http://www.merckmanuals.com/home/eye_disorders/retinal_disorders/detachment_of_the_retina.html)
  • Stickler Involved People: Clinical Characteristics & Diagnostic Criteria (http://sticklers.org/sip2/content/view/17/18/)
  • Stickler Involved People: Stickler Syndrome Recognition, Diagnosis, Treatment (http://www.sticklers.org/sip2/images/stories/SticklerBrochure/sip%20english%20physbrochure%20updated.pdf)

You might also find information on the diagnosis or management of Stickler syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/stickler-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/stickler-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Stickler syndrome?

You may find the following resources about Stickler syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Stickler syndrome?

  • hereditary arthro-ophthalmo-dystrophy
  • hereditary arthro-ophthalmopathy
  • Stickler dysplasia

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Stickler syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Stickler syndrome?

arthritis ; autosomal ; autosomal dominant ; autosomal recessive ; cartilage ; cell ; cleft palate ; collagen ; dysplasia ; gene ; glaucoma ; hereditary ; inheritance ; inherited ; joint ; lower jaw ; micrognathia ; mutation ; myopia ; nearsightedness ; palate ; pattern of inheritance ; recessive ; scoliosis ; short stature ; stature ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Acke FR, Dhooge IJ, Malfait F, De Leenheer EM. Hearing impairment in Stickler syndrome: a systematic review. Orphanet J Rare Dis. 2012 Oct 30;7:84. doi: 10.1186/1750-1172-7-84. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23110709?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/10486316?dopt=Abstract)
  • Baker S, Booth C, Fillman C, Shapiro M, Blair MP, Hyland JC, Ala-Kokko L. A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome. Am J Med Genet A. 2011 Jul;155A(7):1668-72. doi: 10.1002/ajmg.a.34071. Epub 2011 Jun 10. (http://www.ncbi.nlm.nih.gov/pubmed/21671392?dopt=Abstract)
  • Huang F, Kuo HK, Hsieh CH, Lai JP, Chen PK. Visual complications of Stickler syndrome in paediatric patients with Robin sequence. J Craniomaxillofac Surg. 2007 Mar;35(2):76-80. Epub 2007 Apr 18. (http://www.ncbi.nlm.nih.gov/pubmed/17442580?dopt=Abstract)
  • Liberfarb RM, Levy HP, Rose PS, Wilkin DJ, Davis J, Balog JZ, Griffith AJ, Szymko-Bennett YM, Johnston JJ, Francomano CA, Tsilou E, Rubin BI. The Stickler syndrome: genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1. Genet Med. 2003 Jan-Feb;5(1):21-7. Review. Erratum in: Genet Med. 2003 Nov-Dec;5(6):478. (http://www.ncbi.nlm.nih.gov/pubmed/12544472?dopt=Abstract)
  • Nowak CB. Genetics and hearing loss: a review of Stickler syndrome. J Commun Disord. 1998 Sep-Oct;31(5):437-53; 453-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9777489?dopt=Abstract)
  • Poulson AV, Hooymans JM, Richards AJ, Bearcroft P, Murthy R, Baguley DM, Scott JD, Snead MP. Clinical features of type 2 Stickler syndrome. J Med Genet. 2004 Aug;41(8):e107. (http://www.ncbi.nlm.nih.gov/pubmed/15286167?dopt=Abstract)
  • Richards AJ, Baguley DM, Yates JR, Lane C, Nicol M, Harper PS, Scott JD, Snead MP. Variation in the vitreous phenotype of Stickler syndrome can be caused by different amino acid substitutions in the X position of the type II collagen Gly-X-Y triple helix. Am J Hum Genet. 2000 Nov;67(5):1083-94. Epub 2000 Sep 25. (http://www.ncbi.nlm.nih.gov/pubmed/11007540?dopt=Abstract)
  • Snead MP, Yates JR. Clinical and Molecular genetics of Stickler syndrome. J Med Genet. 1999 May;36(5):353-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10353778?dopt=Abstract)
  • Van Camp G, Snoeckx RL, Hilgert N, van den Ende J, Fukuoka H, Wagatsuma M, Suzuki H, Smets RM, Vanhoenacker F, Declau F, Van de Heyning P, Usami S. A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet. 2006 Sep;79(3):449-57. Epub 2006 Jun 26. (http://www.ncbi.nlm.nih.gov/pubmed/16909383?dopt=Abstract)
  • Zechi-Ceide RM, Jesus Oliveira NA, Guion-Almeida ML, Antunes LF, Richieri-Costa A, Passos-Bueno MR. Clinical evaluation and COL2A1 gene analysis in 21 Brazilian families with Stickler syndrome: identification of novel mutations, further genotype/phenotype correlation, and its implications for the diagnosis. Eur J Med Genet. 2008 May-Jun;51(3):183-96. doi: 10.1016/j.ejmg.2007.12.008. Epub 2008 Jan 9. (http://www.ncbi.nlm.nih.gov/pubmed/18276201?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2013
Published: November 24, 2014