Stickler syndrome
Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems.
Overview
Stickler syndrome is a group of hereditary conditions that are characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals, even among members of the same family.
A characteristic feature is a flattened facial appearance resulting from underdeveloped bones in the middle of the face. A group of physical features called Pierre Robin sequence is also common, which includes an opening in the roof of the mouth (a cleft palate), a tongue placed further back than normal (glossoptosis), and a small lower jaw (micrognathia).
Many individuals have severe nearsightedness (high myopia). In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance. Other common eye problems include increased pressure within the eye (glaucoma), clouding of the lens (cataracts), and tearing of the light-sensitive tissue at the back of the eye (retinal detachment).
Hearing loss is also common and may worsen over time. People typically have sensorineural hearing loss (caused by changes in the inner ear) with or without conductive hearing loss (caused by changes in the middle ear).
Most people with Stickler syndrome have joint abnormalities. Arthritis often develops early in life, causing joint pain or stiffness. Affected individuals may also have abnormal curvature of the spine (scoliosis).
Frequency
Stickler syndrome affects an estimated 1 in 7,500 to 9,000 newborns.
Causes
Variants in several genes cause the different types of Stickler syndrome. Approximately 80 percent of people have a variant in the COL2A1 gene, while variants in the COL11A1 gene are the next most common cause.
These are called collagen genes because they provide instructions for making components of collagens, which are complex molecules that give structure and strength to the connective tissues that support the body's joints and organs. Variants in these genes impair the production, processing, or assembly of collagen molecules, leading to the varied features of the syndrome.
Genes Associated with Stickler Syndrome
- COL11A1
- COL11A2
- COL2A1
- COL9A1
- COL9A2
- COL9A3
Inheritance
Most often, Stickler syndrome is inherited in an autosomal dominant pattern, where one copy of the altered gene in each cell is sufficient to cause the disorder. Sometimes, it results from a new (de novo) variant that occurs during the formation of reproductive cells or early embryonic development.
When caused by variants in other genes, it can be inherited in an autosomal recessive pattern, where both copies of the gene in each cell must have a variant to cause the disorder.