Stickler syndrome

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.

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. _ _

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.

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.

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. 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. 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.

Pathogenic variants in the other genes that cause Stickler syndrome ( COL9A1, COL9A2, or COL9A3 are inherited in an autosomal recessive manner. 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: _ _
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• 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.

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.

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.

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.