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Usher syndrome type 1C(USH1C)

MedGen UID:
338506
Concept ID:
C1848604
Disease or Syndrome
Synonyms: Usher syndrome, Acadian variety; USHER SYNDROME, TYPE I, ACADIAN VARIETY
 
Gene (location): USH1C (11p15.1)
 
Monarch Initiative: MONDO:0010171
OMIM®: 276904

Disease characteristics

Excerpted from the GeneReview: Usher Syndrome Type I
Usher syndrome type I (USH1) is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa (RP). Unless fitted with a cochlear implant, individuals do not typically develop speech. RP, a progressive, bilateral, symmetric degeneration of rod and cone functions of the retina, develops in adolescence, resulting in progressively constricted visual fields and impaired visual acuity. [from GeneReviews]
Authors:
Robert K Koenekoop  |  Moises A Arriaga  |  Karmen M Trzupek, et. al.   view full author information

Additional descriptions

From OMIM
Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3; 276902) have progressive hearing loss. For a discussion of genetic heterogeneity of Usher syndrome type I, see USH1 (276900).  http://www.omim.org/entry/276904
From MedlinePlus Genetics
People with Usher syndrome type III experience hearing loss and vision loss beginning somewhat later in life. Unlike the other forms of Usher syndrome, type III is usually associated with normal hearing at birth. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and becomes more severe over time. By middle age, most affected individuals have profound hearing loss. Vision loss caused by retinitis pigmentosa also develops in late childhood or adolescence. Some people with Usher syndrome type III develop vestibular abnormalities that cause problems with balance.

Usher syndrome type II is characterized by hearing loss from birth and progressive vision loss that begins in adolescence or adulthood. The hearing loss associated with this form of Usher syndrome ranges from mild to severe and mainly affects the ability to hear high-frequency sounds. For example, it is difficult for affected individuals to hear 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, and it may become more severe over time. Unlike the other forms of Usher syndrome, type II is not associated with vestibular abnormalities that cause difficulties with balance.

Most individuals with Usher syndrome type I are born with severe to profound hearing loss. Worsening vision loss caused by retinitis pigmentosa becomes apparent in childhood. This type of Usher syndrome also causes abnormalities of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation in space. As a result of the vestibular abnormalities, children with the condition have trouble with balance. They begin sitting independently and walking later than usual, and they may have difficulty riding a bicycle and playing certain sports.

Researchers have identified three major types of Usher syndrome, designated as types I, II, and III. These types are distinguished by the severity of hearing loss, the presence or absence of balance problems, and the age at which signs and symptoms appear. The types are further divided into subtypes based on their genetic cause.

Usher syndrome is a condition characterized by partial or total hearing loss and vision loss that worsens over time. The hearing loss is classified as sensorineural, which means that it is caused by abnormalities of the inner ear. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which 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 break down. Loss of night vision begins first, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. In some cases, vision is further impaired by clouding of the lens of the eye (cataracts). However, many people with retinitis pigmentosa retain some central vision throughout their lives.  https://medlineplus.gov/genetics/condition/usher-syndrome

Clinical features

From HPO
Vestibular hyporeflexia
MedGen UID:
336378
Concept ID:
C1848606
Finding
A general descriptive term that describes impaired functioning of the vestibular apparatus that leads to manifestations such as dizziness or postural imbalance
Congenital sensorineural hearing impairment
MedGen UID:
356101
Concept ID:
C1865866
Disease or Syndrome
A type of hearing impairment caused by an abnormal functionality of the cochlear nerve with congenital onset.
Rod-cone dystrophy
MedGen UID:
1632921
Concept ID:
C4551714
Disease or Syndrome
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

Curated

Bolz HJ, Roux AF
Eur J Hum Genet 2011 Aug;19(8) Epub 2011 Mar 9 doi: 10.1038/ejhg.2011.15. PMID: 21697857Free PMC Article

Recent clinical studies

Diagnosis

Bitner-Glindzicz M, Lindley KJ, Rutland P, Blaydon D, Smith VV, Milla PJ, Hussain K, Furth-Lavi J, Cosgrove KE, Shepherd RM, Barnes PD, O'Brien RE, Farndon PA, Sowden J, Liu XZ, Scanlan MJ, Malcolm S, Dunne MJ, Aynsley-Green A, Glaser B
Nat Genet 2000 Sep;26(1):56-60. doi: 10.1038/79178. PMID: 10973248

Therapy

Nagel-Wolfrum K, Baasov T, Wolfrum U
Adv Exp Med Biol 2014;801:741-7. doi: 10.1007/978-1-4614-3209-8_93. PMID: 24664766
Goldmann T, Overlack N, Wolfrum U, Nagel-Wolfrum K
Hum Gene Ther 2011 May;22(5):537-47. Epub 2011 Mar 25 doi: 10.1089/hum.2010.067. PMID: 21235327

Prognosis

Ouyang XM, Xia XJ, Verpy E, Du LL, Pandya A, Petit C, Balkany T, Nance WE, Liu XZ
Hum Genet 2002 Jul;111(1):26-30. Epub 2002 Jun 18 doi: 10.1007/s00439-002-0736-0. PMID: 12136232
Verpy E, Leibovici M, Zwaenepoel I, Liu XZ, Gal A, Salem N, Mansour A, Blanchard S, Kobayashi I, Keats BJ, Slim R, Petit C
Nat Genet 2000 Sep;26(1):51-5. doi: 10.1038/79171. PMID: 10973247

Clinical prediction guides

Ouyang XM, Xia XJ, Verpy E, Du LL, Pandya A, Petit C, Balkany T, Nance WE, Liu XZ
Hum Genet 2002 Jul;111(1):26-30. Epub 2002 Jun 18 doi: 10.1007/s00439-002-0736-0. PMID: 12136232
Verpy E, Leibovici M, Zwaenepoel I, Liu XZ, Gal A, Salem N, Mansour A, Blanchard S, Kobayashi I, Keats BJ, Slim R, Petit C
Nat Genet 2000 Sep;26(1):51-5. doi: 10.1038/79171. PMID: 10973247
Jain PK, Lalwani AK, Li XC, Singleton TL, Smith TN, Chen A, Deshmukh D, Verma IC, Smith RJ, Wilcox ER
Genomics 1998 Jun 1;50(2):290-2. doi: 10.1006/geno.1998.5320. PMID: 9653658

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