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Disease Profile

Usher 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

Childhood

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ICD-10

H35.5

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.

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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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Other names (AKA)

Deafness-retinitis pigmentosa syndrome; Dystrophia retinae pigmentosa-dysostosis syndrome; Graefe-Usher syndrome;

Categories

Eye diseases

Summary

Usher syndrome is a genetic disorder characterized by sensorineural hearing loss or deafness and progressive vision loss due to retinitis pigmentosa. Sensorineural hearing means it is caused by abnormalities of the inner ear. Retinitis pigmentosa is an eye disease that affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. Night vision loss begins first, followed by blind spots that develop in the side (peripheral) vision, that can enlarge and merge to produce tunnel vision (loss of all peripheral vision). In some cases, vision is further impaired by clouding of the lens of the eye (cataracts). Three major types of Usher syndrome have been described types I, II, and III. The different types are distinguished by their severity and the age when signs and symptoms appear. All three types are inherited in an autosomal recessive manner.[1] Treatment for the hearing loss may include hearing aids or surgery for a cochlear implant. Vitamin A palmitate is useful for treating the vision loss in people with Usher syndrome type II.[2]

Symptoms

Researchers have identified three major types of Usher syndrome, designated as types I, II, and III. These types are distinguished mainly by their severity, and the age when signs and symptoms appear. These types are also further divided into subtypes.[1]

Usher syndrome type I characterized by:

  • Severe hearing loss or deafness at birth or developing within the first year of life
  • Progressive visions loss, starting during infancy, caused by retinitis pigmentosa
  • Balance and equilibrium issues due to problems within the vestibular system (the sensory apparatus of the inner ear that helps the body maintain its postural equilibrium)
  • Motor delay, manifested by children sitting independently and walking later than usual.

Usher syndrome type II characterized by: 

  • Hearing loss  from birth, usually milder than type I and mainly affects high tones. Children with Usher syndrome type II have problems hearing high, soft, speech sounds such as those of the letters "d" and "t." The degree of hearing loss varies within and among families with this condition. 
  • Progressive vision loss that begins in adolescence or adulthood.
  • Absence of any balance or equilibrium problems.

Usher syndrome type III characterized by: 

  • Progressive hearing loss which begins during the first few decades of life. Therefore, unlike the other forms of Usher syndrome, infants with Usher syndrome type III are usually born with normal hearing. Hearing loss typically begins during the first two decades of life, after the development of speech, and progresses over time. By middle age, most affected individuals are profoundly deaf.
  • Progressive vision loss developing in late childhood or adolescence.
  • Variable balance issues, due to vestibular system problems.

For additional information about subypes please visit the OMIM phenotype series link: https://www.omim.org/phenotypicSeries/PS276900

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 electroretinogram
0000512
Abnormality of retinal pigmentation
0007703
Blindness
0000618
Nyctalopia
Night blindness
Night-blindness
Poor night vision

[ more ]

0000662
Progressive visual loss
Progressive loss of vision
Progressive vision loss
Progressive visual impairment
Slowly progressive visual loss
Vision loss, progressive
Visual loss, progressive

[ more ]

0000529
Sensorineural hearing impairment
0000407
Vestibular areflexia
0008568
Visual field defect
Partial loss of field of vision
0001123
30%-79% of people have these symptoms
Ataxia
0001251
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
High hypermetropia
Severe farsightedness
Severe long-sightedness

[ more ]

0008499
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
5%-29% of people have these symptoms
Abnormal cardiovascular system physiology
0011025
Abnormality of dental color
Abnormality of tooth color
Abnormality of tooth shade

[ more ]

0011073
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality

[ more ]

0000682
Anxiety
Excessive, persistent worry and fear
0000739
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum

[ more ]

0007360
Astigmatism
Abnormal curving of the cornea or lens of the eye
0000483
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Decreased fertility
Abnormal fertility
0000144
Depressivity
Depression
0000716
EMG abnormality
0003457
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hyperacusis
0010780
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Microdontia
Decreased width of tooth
0000691
Myopathy
Muscle tissue disease
0003198
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Psychosis
0000709
Tinnitus
Ringing in ears
Ringing in the ears

[ more ]

0000360

Cause

Usher syndrome is an inherited disorder with different subtypes caused by mutations in any of a number of genes:[3][4][5][6][7] 

Type I is divided in the following subtypes:

  • IB, caused by mutations in the MYO7A gene (the most common one)
  • IC, caused by mutations in the USH1C gene
  • ID, caused by mutations in the CDH23 gene
  • ID-F, caused by mutations in the PCDH15 and CDH23 genes
  • IF, caused by mutations in the PCDH15 gene
  • IG, caused by mutations in the SANS gene
  • IH, caused by mutations in the USH1H gene
  • IJ, caused by mutations in the CIB2 gene 
  • IK, caused by mutations in the USH1K gene

Type II is divided in the following subtypes:

  • IIA, caused by mutations in the USH2A gene
  • IIC, caused by mutations in the ADGRV1 gene
  • IID, caused by mutations in the WHRN gene
  • IIC, GPR98/PDZD7, caused by mutations in the ADGRV1 (ADGRV1 is also known as GPR98) and PDZD7 genes

Type III is divided in the following subtypes:

  • IIIA, caused by mutations in the CLRN1 gene
  • IIIB, caused by mutations in the HARS gene

Please see the list of the different types and subtypes of Usher syndrome and their specific gene mutations provided by OMIM.

Many of the genes related to Usher syndrome give instructions to make proteins needed for normal hearing, balance, and vision. The signs and symptoms of Usher syndrome occur when these genes have mutations that impair how they function. In some cases, the exact role of the genes involved is unknown. In some cases no mutation is identified, and it is believed that other genes may be involved.[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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Usher syndrome. This website is maintained by the National Library of Medicine.
      • The National Institute on Deafness and Other Communication Disorders (NIDCD) conducts and supports biomedical and behavioral research and research training in the normal and disordered processes of hearing, balance, smell, taste, voice, speech, and language. Click on the link to view information on this topic.
      • 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

        • 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.
        • The 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 Usher 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 Usher syndrome. Click on the link to view a sample search on this topic.

          References

          1. Usher syndrome. Genetics Home Reference (GHR). 2016; https://ghr.nlm.nih.gov/condition/usher-syndrome.
          2. Keats BJB & Lentz J. Usher Syndrome Type II. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK1341/.
          3. Bonnet C, El-Amraoui A. Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches. Curr Opin Neurol. February 2012; 25(1):42-49.
          4. Cassandra L. Kniffin. USHER SYNDROME, TYPE IJ; USH1J. OMIM. 2014; https://omim.org/entry/614869.
          5. Cassandra L. Kniffin. USHER SYNDROME, TYPE IIC; USH2C. OMIM. 2016; https://omim.org/entry/605472.
          6. Cassandra L. Kniffin. USHER SYNDROME, TYPE IG; USH1G. OMIM. 2014; https://omim.org/entry/606943.
          7. Cassandra L. Kniffin. USHER SYNDROME, TYPE IID; USH2D. OMIM. 2014; https://omim.org/entry/611383.

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