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Disease Profile

Stickler syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Categories

Congenital and Genetic Diseases

Summary

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: COL2A1COL11A1, COL11A2, COL9A1COL9A2, or COL9A3The 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]

Symptoms

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]

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.

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

Cause

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]

Diagnosis

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]

Treatment

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]

Organizations

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

      Learn more

      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.

          References

          1. Robin NH, Moran RT, and Ala-Kokko L. Stickler Syndrome. GeneReviews. March 16, 2017; https://www.ncbi.nlm.nih.gov/books/NBK1302/.
          2. Stickler syndrome. Genetics Home Reference. March 2016; https://ghr.nlm.nih.gov/condition/stickler-syndrome.
          3. Le Merrer M. Stickler syndrome. Orphanet. November 2008; https://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.

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