Stickler Syndrome

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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 Robin sequence, is common in children with Stickler syndrome. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue, and a small lower jaw. This combination of features can lead to feeding problems and difficulty breathing.

Many people with Stickler syndrome have severe nearsightedness (high myopia). In some types of this condition, the jelly-like substance within the eye (the vitreous) has an abnormal appearance. Other eye problems are also common, including increased pressure within the eye (glaucoma) and tearing of the lining of the eye (retinal detachment). These eye abnormalities can cause impaired vision or blindness in some cases.

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

Most people with Stickler syndrome have skeletal abnormalities that affect the joints. For example, 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.

Researchers have described three 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. One type, often called non-ocular Stickler syndrome, does not affect the eyes.

Like Stickler syndrome, a condition called Marshall syndrome is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Whether Marshall syndrome represents a variant form 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 COL11A1, COL11A2, and COL2A1 genes cause Stickler syndrome.

The COL2A1, COL11A1, and COL11A2 genes are involved in the production of type II and type XI collagen. Collagens are complex molecules that provide structure and strength to tissues that support the body's joints and organs (connective tissues). Type II and type XI collagen are components of cartilage, vitreous, and other connective tissues.

Mutations in any one of these genes impair the production, processing, or assembly of type II 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 three known genes. Researchers believe that mutations in other genes may be responsible for this condition, but those genes have not been identified.

Marshall syndrome results from mutations in the COL11A1 gene.

How do people inherit Stickler syndrome?

Stickler syndrome is 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 in the COL2A1, COL11A1, or COL11A2 gene. These cases occur in people with no history of Stickler syndrome in their family.

Marshall syndrome also has an autosomal dominant pattern of inheritance.

Source: National Institutes of Health

Report summarizes life sciences therapy study findings from University of Oulu

"A splice site alteration (involving introns 47-55) was present in seven cases, with one in intron 50 (c.3816 + 1G >A) occurring in three patients. Two patients had a different deletion, and a missense mutation (Gly1471Asp) was observed in one case. In 4/10 patients the phenotype was classified as Marshall syndrome because of early-onset severe hearing loss and characteristic facial features. These four patients were all heterozygous for a splice site mutation in intron 50. One of these cases had a type 1 vitreous anomaly despite the presence of a COL11A1 mutation. The remaining 6/10 patients had an overlapping Marshall-Stickler phenotype with less pronounced facial features," wrote M. Majava and colleagues, University of Oulu.

The researchers concluded: "None of these had a mutation in the hot spot region of intron 50."

Majava and colleagues published their study in American Journal of Medical Genetics Part A (A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies. American Journal of Medical Genetics Part A, 2007;143(3):258-64).

For additional information, contact M. Majava, University of Oulu, University of Oulu, Biocenter, Oulu, Oulu, Finland.

Publisher contact information for the American Journal of Medical Genetics Part A is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Keywords: Finland, Oulu, Life Sciences Therapy, Interferon Alfa-2b, Intron, Pharmaceuticals, Drugs, Therapy, Treatment.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.