Usher Syndrome Health Article

Genetic profile

Usher syndrome is inherited in an autosomal recessive manner. "Autosomal" means that males and females are equally likely to be affected. "Recessive" refers to a specific type of inheritance in which both copies of a person's gene pair (i.e. both alleles) need to have a change or "mutation" in order for the disease to develop. In this situation, an affected individual receives a mutated copy of the same gene from each parent. If the parents are not affected, they each have one working copy of the gene and one non-working (mutated) copy, and are only "carriers" for Usher syndrome. The chance that two carrier parents will have a child affected with Usher syndrome is 25% for each pregnancy. They also have a 50% chance to have an unaffected child who is simply a carrier, and a 25% chance to have an unaffected child who is not a carrier, with each pregnancy. In the United States, as many as one in every 70 people may be carriers of a mutation that can lead to Usher syndrome.

Although there are three recognizable types of Usher syndrome (I, II, and III), genetic research has shown that there are numerous genes, located on different chromosomes, that can all lead to Usher syndrome. This indicates that there is genetic heterogeneity among different families with Usher syndrome, meaning that different genes can lead to the same or similar disease among different families. As of February 2001, researchers have identified six different subtypes of Usher syndrome type I (USH1A, USH1B, USH1C, USH1D, USH1E, and USH1F), four subtypes of Usher syndrome type II (USH 2A, USH2B, USH2C, and USH2D), and one type of Usher syndrome type III (USH3). Although specific genes have been identified for only four of the 11 subtypes, the other seven have been linked to specific chromosomal regions.

Genetic Classification of Usher syndrome—February, 2001

• USH1A—Located on chromosome 14q32. Specific gene unknown.
• USH1B—Located on chromosome 11q13.5. Specific gene called myosin VIIA.
• USH1C—Located on chromosome 11p15.1. Specific gene called harmonin.
• USH1D—Located on chromosome 10q21-22. Specific gene called CDH23.
• USH1E—Located on chromosome 21q21. Specific gene unknown.
• USH1F—Located on chromosome 10. Specific gene unknown.
• USH2A—Located on chromosome 1q41. Specific gene called usherin.
• USH2B—Located on chromosome 3p23-24.2. Specific gene unknown.
• USH2C—Located on chromosome 5q14.3-21.3. Specific gene unknown.
• USH2D—Chromosome location unknown. Specific gene unknown.
• USH3—Located on chromosome 3q21-25. Specific gene unknown.

Although specific genes have been identified for some of the Usher syndrome subtypes (i.e. myosin VIIA, harmonin, CDH23, and usherin), not all mutations in these genes lead specifically to Usher syndrome. For example, although mutations in CDH23 can lead to Usher syndrome type 1D, some people who have certain types of mutations in both of their CDH23 gene copies have a form of autosomal recessive deafness (called DFNB12) in which affected individuals have profound SNHL at birth, but do not have balance or vision changes that are typically seen in Usher syndrome.

Demographics

It is estimated that 2.5-4.5 per 100,000 people are affected with Usher syndrome in various countries, including the United States, Denmark, Sweden, Norway, Finland, and Columbia, although it has been diagnosed in other parts of the world as well. There are some areas where Usher syndrome seems to be more common, including communities in northern Sweden and among the French Acadians in Louisiana. Certain types of Usher syndrome are more common in certain areas of the world as well. For example, among affected people in Finland, approximately 40% have type III. However, in the United States, types I and II are most common and occur with nearly equal frequency, while type III is very rare.

Signs and symptoms

Symptoms of Usher syndrome type I:

• Profound hearing loss at birth, causing lack of speech
• Lack of vestibular function at birth, leading to delayed ability to walk and increased clumsiness
• Retinitis pigmentosa in childhood, causing night blindness, tunnel vision and decreased vision over time
• May cause mental retardation or psychiatric problems in some people

Symptoms of Usher syndrome type II:

• Mild to severe hearing loss (for low-frequency sound) and profound hearing loss (for high-frequency sound) at birth
• Normal vestibular function, resulting in normal ability to maintain balance
• Retinitis pigmentosa in teens or early adult years, causing night blindness, tunnel vision and decreased vision over time
• May cause mental retardation or psychiatric problems in some people

Symptoms of Usher syndrome type III:

• Normal hearing or mild hearing loss at birth that worsens over time
• Abnormal vestibular function, causing mild balance problems that worsen over time
• Retinitis pigmentosa by teenage or early adult years, causing night blindness, tunnel vision and decreased vision over time
• May cause mental retardation or psychiatric problems in some people