Usher Syndrome

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Annotated Information

Classification and Resources

ID 130
ICD-10 ICD10CM:H35.5;
ICD-9-CM
OMIM OMIM:276900;OMIM:276901;OMIM:276902;OMIM:276904;OMIM:601067;OMIM:602083;OMIM:602097;OMIM:605472;OMIM:606943;OMIM:611383;OMIM:612632;OMIM:614504;OMIM:614869;OMIM:614990;
SNOMED-CT
Orphanet
MeSH MSH:D052245;
DO

Defination

Usher syndrome is a relatively rare genetic disorder caused by a mutation in any one of genes resulting in a combination of hearing loss and visual impairment, and is a leading cause of deafblindness Usher syndrome is incurable at present~Other names for Usher syndrome include Hallgren syndrome, Usher-Hallgren syndrome, retinitis pigmentosa-dysacusis syndrome, and dystrophia retinae dysacusis syndrome~

Synonyms

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Etiology

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Diagnosis

Since Usher syndrome is incurable at present, it is helpful to diagnose children well before they develop the characteristic night blindness Some preliminary studies have suggested as many as % of congenitally deaf children may have Usher syndrome However, a misdiagnosis can have bad consequences~The simplest approach to diagnosing Usher syndrome is to test for the characteristic chromosomal mutations An alternative approach is electroretinography, although this is often disfavored for children, since its discomfort can also make the results unreliable Parental consanguinity is a significant factor in diagnosis Usher syndrome I may be indicated if the child is profoundly deaf from birth and especially slow in walking~Thirteen other syndromes may exhibit signs similar to Usher syndrome, including Alport syndrome, Alstrom syndrome, Bardet-Biedl syndrome, Cockayne syndrome, spondyloepiphyseal dysplasia congenita, Flynn-Aird syndrome, Friedreich ataxia, Hurler syndrome (MPS-), Kearns-Sayre syndrome (CPEO), Norrie syndrome, osteopetrosis (Albers-Schonberg disease), Refsum's disease (phytanic acid storage disease), and Zellweger syndrome (cerebrohepatorenal syndrome)~

Symptoms

Since Usher syndrome is incurable at present, it is helpful to diagnose children well before they develop the characteristic night blindness Some preliminary studies have suggested as many as % of congenitally deaf children may have Usher syndrome However, a misdiagnosis can have bad consequences~The simplest approach to diagnosing Usher syndrome is to test for the characteristic chromosomal mutations An alternative approach is electroretinography, although this is often disfavored for children, since its discomfort can also make the results unreliable Parental consanguinity is a significant factor in diagnosis Usher syndrome I may be indicated if the child is profoundly deaf from birth and especially slow in walking~Thirteen other syndromes may exhibit signs similar to Usher syndrome, including Alport syndrome, Alstrom syndrome, Bardet-Biedl syndrome, Cockayne syndrome, spondyloepiphyseal dysplasia congenita, Flynn-Aird syndrome, Friedreich ataxia, Hurler syndrome (MPS-), Kearns-Sayre syndrome (CPEO), Norrie syndrome, osteopetrosis (Albers-Schonberg disease), Refsum's disease (phytanic acid storage disease), and Zellweger syndrome (cerebrohepatorenal syndrome)~

Treatment

Usher syndrome is responsible for the majority of deaf-blindness The word syndrome means that multiple symptoms occur together, in this case, deafness and blindness It occurs in roughly person in , in the United States, in , in Norway and in , in Germany People with Usher syndrome represent roughly one-sixth of people with retinitis pigmentosa~Usher syndrome is inherited in an autosomal recessive pattern "Recessive" means both parents must contribute an appropriate gene for the syndrome to appear, and "autosomal" means the gene is not carried on one of the sex chromosomes (X or Y), but rather on one of the other pairs (See the article on human genetics for more details)~The progressive blindness of Usher syndrome results from retinitis pigmentosa The photoreceptor cells usually start to degenerate from the outer periphery to the center of the retina, including the macula The degeneration is usually first noticed as night blindness (nyctalopia); peripheral vision is gradually lost, restricting the visual field (tunnel vision), which generally progresses to complete blindness The qualifier 'pigmentosa' reflects the fact that clumps of pigment may be visible by an ophthalmoscope in advanced stages of degeneration~Although Usher syndrome has been classified clinically in several ways, the prevailing approach is to classify it into three clinical sub-types called Usher I, II and III in order of decreasing severity of deafness Usher I and II are the more common forms; the fraction of people with Usher III is significant only in a few specific areas, such as Finland and Birmingham As described below, these clinical subtypes may be further subdivided by the particular gene mutated; people with Usher I and II may have any one of six and three genes mutated, respectively, whereas only one gene has been associated with Usher III The function of these genes is still poorly understood The hearing impairment associated with Usher syndrome is better understood: damaged hair cells in the cochlea of the inner ear inhibit electrical impulses from reaching the brain~Usher syndrome I[edit]~People with Usher I are usually born deaf and often have difficulties in maintaining their balance owing to problems in the vestibular system Babies with Usher I are usually slow to develop motor skills such as walking Worldwide, the estimated prevalence of Usher syndrome type I is to per , people in the general population~Usher syndrome type I can be caused by mutations in any one of several different genes: CDH, MYOA, PCDH, USHC, and USHG These genes function in the development and maintenance of inner ear structures such as hair cells (stereocilia), which transmit sound and motion signals to the brain Alterations in these genes can cause an inability to maintain balance (vestibular dysfunction) and hearing loss The genes also play a role in the development and stability of the retina by influencing the structure and function of both the rod photoreceptor cells and supporting cells called the retinal pigmented epithelium Mutations that affect the normal function of these genes can result in retinitis pigmentosa and resultant vision loss~Type I has been found to be more common in people of Ashkenazi Jewish ancestry (central and eastern European) and in the French-Acadian populations (Louisiana)~Usher syndrome II[edit]~People with Usher II are generally hard-of-hearing rather than deaf, and their hearing does not degrade over time; moreover, they generally have a normal vestibular system Usher syndrome type II occurs at least as frequently as type I, but because type II may be underdiagnosed or more difficult to detect, it could be up to three times as common as type I~Usher syndrome type II may be caused by mutations in any of three different genes: USHA, GPR, and DFNB The protein encoded by the USHA gene, usherin, is located in the supportive tissue in the inner ear and retina Usherin is critical for the proper development and maintenance of these structures, which may help explain its role in hearing and vision loss The location and function of the other two proteins are not yet known~Usher syndrome III[edit]~By contrast, people with Usher III experience a 'progressive' loss of hearing and roughly half have vestibular dysfunction The frequency of Usher syndrome type III is highest in the Finnish population, but it has been noted rarely in a few other ethnic groups~Mutations in only one gene, CLRN, have been linked to Usher syndrome type III CLRN encodes clarin-, a protein important for the development and maintenance of the inner ear and retina However, the protein's function in these structures, and how its mutation causes hearing and vision loss, is still poorly understood~

Labs working on this disease

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References

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