National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Stickler syndrome

Stickler syndrome is a group of hereditary connective tissue disorders characterized by distinctive facial features, eye abnormalities, hearing loss, and joint problems. The symptoms of Stickler syndrome may vary but include near-sightedness (myopia), retinal detachment, underdevelopment of the middle of the face, and the development of arthritis at a young age.[1]

Stickler syndrome is caused by genetic changes (mutations or pathogenic variants) in one of six genes: COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, or COL9A3. The syndrome can be inherited in an autosomal dominant or autosomal recessive manner. Stickler syndrome can be diagnosed when a doctor observes many symptoms consistent with the syndrome. Genetic testing can be used to confirm the diagnosis. Treatment for Stickler syndrome may include surgeries, medications to reduce joint pain, and hearing aids.[1]

Last updated: 3/1/2018
The signs and symptoms of Stickler syndrome may include distinctive facial features, eye abnormalities, hearing loss, and symptoms affecting the joints. Facial features common to people who have Stickler syndrome may include being born with a cleft palate, having a small chin (micrognathia), and having a tongue that is placed further back in the mouth (glossoptosis). These features together are known as Pierre-Robin sequence. In some cases, these facial features may make it difficult for babies with Stickler syndrome to breathe or eat. People with Stickler syndrome may also have underdevelopment of the middle of the face (midface hypoplasia).[2][3] 

Eye abnormalities associated with Stickler syndrome may include extreme near-sightedness (myopia). This can cause an increased risk for retinal detachment or the development of clouding of the lens (cataracts).[1] These problems can lead to vision loss in some cases.[2] People with Stickler syndrome may also have some hearing loss.[1]

Stickler syndrome can cause people to have joint problems. Children with this syndrome may experience loose joints (joint laxity) or may be very flexible. Some people may develop arthritis at a young age, typically before 40-years-old. Other signs may include a curvature of the spine (scoliosis) or having flat vertebrae (platyspondyly). These features can cause back pain for some people.[1][2] People with Stickler syndrome may also have weakened bones (osteoporosis), which can cause an increased risk for bone fractures.[4][5]

Other signs of Stickler syndrome may include an increased risk for the valves in the heart to close improperly (mitral valve prolapse).[1]
Last updated: 3/1/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 75 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal vitreous humor morphology 0004327
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Arthralgia
Joint pain
0002829
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion
[ more ] 		0000327
Long philtrum 0000343
Malar flattening
Zygomatic flattening
0000272
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness
[ more ] 		0000545
Retinal detachment
Detached retina
0000541
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
Skeletal dysplasia 0002652
Telecanthus
Corners of eye widely separated
0000506
30%-79% of people have these symptoms
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] 		0000463
Arachnodactyly
Long slender fingers
Spider fingers
[ more ] 		0001166
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Astigmatism
Abnormal curving of the cornea or lens of the eye
0000483
Bone pain 0002653
Chronic otitis media
Chronic infections of the middle ear
0000389
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Depressed nasal ridge
Flat nose
Recessed nasal ridge
[ more ] 		0000457
Disproportionate tall stature 0001519
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn
[ more ] 		0002020
Genu valgum
Knock knees
0002857
Glossoptosis
Retraction of the tongue
0000162
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Kyphosis
Hunched back
Round back
[ more ] 		0002808
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ] 		0000158
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Mitral valve prolapse 0001634
Muscular hypotonia
Low or weak muscle tone
0001252
Osteoarthritis
Degenerative joint disease
0002758
Pectus carinatum
Pigeon chest
0000768
Platyspondyly
Flattened vertebrae
0000926
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes
[ more ] 		0000520
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
Scoliosis 0002650
Sensorineural hearing impairment 0000407
5%-29% of people have these symptoms
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality
[ more ] 		0000682
Advanced eruption of teeth
Early eruption of teeth
0006288
Blindness 0000618
Cachexia
Wasting syndrome
0004326
Conductive hearing impairment
Conductive deafness
Conductive hearing loss
[ more ] 		0000405
Ectopia lentis 0001083
Feeding difficulties in infancy 0008872
Glaucoma 0000501
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hip dislocation
Dislocated hips
Dislocation of hip
[ more ] 		0002827
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Open bite
Absence of overlap of upper and lower teeth
Open bite between upper and lower teeth
[ more ] 		0010807
Protrusio acetabuli 0003179
Reduced bone mineral density
Low solidness and mass of the bones
0004349
Reduced number of teeth
Decreased tooth count
0009804
Short hard palate 0010290
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ] 		0003202
Slender build
Thin build
0001533
Spinal canal stenosis
Narrow spinal canal
0003416
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Uveitis 0000554
1%-4% of people have these symptoms
Bifid uvula 0000193
Morbus Scheuermann 0010891
Spondylolisthesis
Displacement of one backbone compared to another
Slipped backbone
[ more ] 		0003302
Submucous cleft hard palate 0000176
Percent of people who have these symptoms is not available through HPO
Arthropathy
Disease of the joints
0003040
Autosomal dominant inheritance 0000006
Beaking of vertebral bodies 0004568
Irregular femoral epiphysis
Irregular thighbone end part
0006361
Membranous vitreous appearance 0031153
Pectus excavatum
Funnel chest
0000767
Pierre-Robin sequence 0000201
Spondyloepiphyseal dysplasia 0002655
Showing of 75 |
Last updated: 7/1/2020
Stickler syndrome is caused by genetic changes (mutations or pathogenic variants) in one of six genes: COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, or COL9A3. These genes are all responsible for providing instructions to the body to produce collagen. Collagen is involved in providing length and structure to tissues in the body known as connective tissues. Connective tissues are present in many parts of the body including the eyes, skin, and joints. When there are pathogenic variants in any of the genes associated with Stickler syndrome, it causes the collagen in the body to not be made or processed properly. This causes the signs and symptoms associated with Stickler syndrome.[2]

In some cases, people who have symptoms of Stickler syndrome have genetic testing that does not identify the pathogenic variant that is causing the syndrome. Therefore, researchers think that there might be other genes in which pathogenic variants cause Stickler syndrome, but these genes have not yet been identified.[1][2]
Last updated: 3/1/2018
Stickler syndrome can be inherited in an autosomal dominant manner or in an autosomal recessive manner depending on the gene that has a change (mutation or pathogenic variant).

When Stickler syndrome is caused by pathogenic variants in COL2A1, COL11A1, or COL11A2, it is inherited in an autosomal dominant manner.[1] This means that only one copy of one of the genes causing Stickler syndrome has a pathogenic variant. We inherit one copy of every gene from our mother and the other from our father. When a person who has Stickler syndrome has children, for each child there is a:
  • 50% chance that the child will inherit the gene with a pathogenic variant, meaning he or she will have Stickler syndrome
  • 50% chance that the child will inherit the working copy of the gene, meaning he or she will not have Stickler syndrome
In some cases, people who have an autosomal dominant form of Stickler syndrome are the first people to be diagnosed in the family. This may be because they inherited the genetic change from a parent, but the parent has mild symptoms of the syndrome and was never diagnosed. Most people who have an autosomal dominant form of Stickler syndrome inherited the genetic change from a parent.[1] In other cases, the genetic change may be new in the person who was diagnosed with Stickler syndrome. Genetic changes that are new in a person are called de novo.[1]

Pathogenic variants in the other genes that cause Stickler syndrome (COL9A1, COL9A2, or COL9A3 are inherited in an autosomal recessive manner.[1] This means that both copies of one of these genes must have a pathogenic variant for a person to have signs of Stickler syndrome. People who only have one changed copy of a gene that causes an autosomal recessive form of Stickler syndrome are known as carriers. Carriers do not have signs or symptoms of the syndrome. When two carriers of Stickler syndrome have children together, for each child there is a:
  • 25% chance that the child will inherit both changed copies of the gene, so he or she has Stickler syndrome
  • 50% chance that the child will inherit only one changed copy of the gene, so he or she is a carrier of the syndrome like each of the parents
  • 25% chance that the child will inherit both working copies of the gene, so he or she does not have Stickler syndrome and is not a carrier of the syndrome
Stickler syndrome shows a characteristic known as variable expressivity. This means that people with Stickler syndrome can have different signs and symptoms of the syndrome, even among members of the same family. However, anyone with a pathogenic variant that causes Stickler syndrome is expected to have some symptoms of the syndrome. This is called full penetrance.[1]
Last updated: 3/1/2018
Stickler syndrome is suspected when a doctor observes signs or symptoms such as distinctive facial features, symptoms affecting the eyes, hearing loss, joint problems, and other people in the family with similar symptoms. The diagnosis can be confirmed by comparing the features seen in the person to the features seen in people who have Stickler syndrome. A set of criteria has been published to help doctors determine if a person should be diagnosed with Stickler syndrome based on his or her signs and symptoms.[1]

Some people with Stickler syndrome may decide to have genetic testing to confirm the diagnosis. This can allow other family members to have testing for Stickler syndrome. It can also provide information about the inheritance pattern so that the chances for future children to have Stickler syndrome can be better understood.[1]
Last updated: 3/1/2018
After a person is diagnosed with Stickler syndrome, some evaluations may be recommended to determine if there are other signs of the syndrome that have not been previously noticed. These evaluations may include an eye exam, exam by a doctor who can check for facial differences such as cleft palate (craniofacial specialist), a hearing (audiometry) exam, and an evaluation for any possible heart problems.[1]

Treatment for Stickler syndrome is aimed at treating the specific symptoms each person has. For some, this may involve surgeries to correct cleft palate or retinal detachment. Other treatments may include hearing aids for hearing loss or medications for joint pain.[1]
Last updated: 3/1/2018
Because the symptoms of Stickler syndrome are variable, it can be difficult to predict what the long-term outlook is for people who have the syndrome. There is an increased risk for eye problems associated with Stickler syndrome including retinal detachment and cataracts. These symptoms can lead to vision loss. People with Stickler syndrome may also experience arthritis before 40-years-old. In general, people with Stickler syndrome have typical intelligence and can function well in society. Some people do not know they have Stickler syndrome until another family member is diagnosed because the symptoms can be relatively mild.[1]
Last updated: 3/1/2018

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • The The Marfan Foundation has a Directory of Medical Institutions which is comprised of institutions throughout the United States that treat Marfan syndrome and related conditions.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Stickler syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Stickler syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Stickler syndrome in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Stickler syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Robin NH, Moran RT, and Ala-Kokko L. Stickler Syndrome. GeneReviews. March 16, 2017; http://www.ncbi.nlm.nih.gov/books/NBK1302/.
  2. Stickler syndrome. Genetics Home Reference. March 2016; http://ghr.nlm.nih.gov/condition/stickler-syndrome.
  3. Le Merrer M. Stickler syndrome. Orphanet. November 2008; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=828.
  4. Vogiatzi MG, Li D, Tian L, Garifallou JP, Kim CE, Hakonarson H, and Levine MA. A novel dominant COL11A1 mutation in a child with Stickler syndrome type II is associated with recurrent fractures. Osteoporosis International. January 2018; 29(1):247-251. https://www.ncbi.nlm.nih.gov/pubmed/28971234.
  5. Insalaco P, Legrand E, Bouvard B, and Audran M. Osteoporosis in Stickler syndrome: A new family case with bone histology study. Morphologie. March 2017; 101(332):33-38. https://www.ncbi.nlm.nih.gov/pubmed/28159459.