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Usher syndrome type 2A(USH2A)

MedGen UID:
338513
Concept ID:
C1848634
Disease or Syndrome
Synonyms: RETINAL DISEASE IN USHER SYNDROME TYPE IIA, MODIFIER OF; USHER SYNDROME, TYPE IIA
 
Genes (locations): PDZD7 (10q24.31); USH2A (1q41)
 
Monarch Initiative: MONDO:0010169
OMIM®: 276901

Disease characteristics

Excerpted from the GeneReview: Usher Syndrome Type II
Usher syndrome type II (USH2) is characterized by the following: Congenital, bilateral sensorineural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies. Intact or variable vestibular responses. Retinitis pigmentosa (RP); progressive, bilateral, symmetric retinal degeneration that begins with night blindness and constricted visual fields (tunnel vision) and eventually includes decreased central visual acuity; the rate and degree of vision loss vary within and among families. [from GeneReviews]
Authors:
Robert Koenekoop  |  Moises Arriaga  |  Karmen M Trzupek, et. al.   view full author information

Additional descriptions

From OMIM
Usher syndrome (USH) is a clinically and genetically heterogeneous autosomal recessive disorder characterized by sensorineural hearing deficiencies at birth and later development of progressive retinitis pigmentosa (RP). It is the most frequent cause of combined deafness and blindness in adults and affects 3 to 6% of children born with hearing impairment. In brief, patients with Usher syndrome type II (USH2) have mild hearing impairment with normal vestibular responses. Type II is the most common of the 3 types of Usher syndrome (Eudy et al., 1998). See 276900 for clinical characterization of Usher syndrome types I, II, and III. Genetic Heterogeneity of Usher Syndrome Type II Usher syndrome type II is genetically heterogeneous. USH2C (605472) is caused by mutation in the ADGRV1 gene (602851) or by biallelic digenic mutation in the ADGRV1 and PDZD7 (612971) genes. USH2D (611383) is caused by mutation in the WHRN gene (607928). The locus designation USH2B has been withdrawn; see HISTORY.  http://www.omim.org/entry/276901
From MedlinePlus Genetics
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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/usher-syndrome

Clinical features

From HPO
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.

Professional guidelines

PubMed

Stephenson KAJ, Whelan L, Zhu J, Dockery A, Wynne NC, Cairns RM, Kirk C, Turner J, Duignan ES, O'Byrne JJ, Silvestri G, Kenna PF, Farrar GJ, Keegan DJ
Invest Ophthalmol Vis Sci 2023 Jul 3;64(10):23. doi: 10.1167/iovs.64.10.23. PMID: 37466950Free PMC Article
Zaw K, Carvalho LS, Aung-Htut MT, Fletcher S, Wilton SD, Chen FK, McLenachan S
Asia Pac J Ophthalmol (Phila) 2022 Jul-Aug 01;11(4):369-379. Epub 2022 Aug 17 doi: 10.1097/APO.0000000000000546. PMID: 36041150
Ivanova ME, Trubilin VN, Atarshchikov DS, Demchinsky AM, Strelnikov VV, Tanas AS, Orlova OM, Machalov AS, Overchenko KV, Markova TV, Golenkova DM, Anoshkin KI, Volodin IV, Zaletaev DV, Pulin AA, Nadelyaeva II, Kalinkin AI, Barh D
Ophthalmic Genet 2018 Dec;39(6):706-713. Epub 2018 Oct 25 doi: 10.1080/13816810.2018.1532527. PMID: 30358468

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

Etiology

Stephenson KAJ, Whelan L, Zhu J, Dockery A, Wynne NC, Cairns RM, Kirk C, Turner J, Duignan ES, O'Byrne JJ, Silvestri G, Kenna PF, Farrar GJ, Keegan DJ
Invest Ophthalmol Vis Sci 2023 Jul 3;64(10):23. doi: 10.1167/iovs.64.10.23. PMID: 37466950Free PMC Article
Daich Varela M, Wong SW, Kiray G, Schlottmann PG, Arno G, Shams ANA, Mahroo OA, Webster AR, AlTalbishi A, Michaelides M
Am J Ophthalmol 2023 Dec;256:186-195. Epub 2023 Jul 7 doi: 10.1016/j.ajo.2023.06.026. PMID: 37422204
Karali M, Testa F, Di Iorio V, Torella A, Zeuli R, Scarpato M, Romano F, Onore ME, Pizzo M, Melillo P, Brunetti-Pierri R, Passerini I, Pelo E, Cremers FPM, Esposito G, Nigro V, Simonelli F, Banfi S
Sci Rep 2022 Dec 2;12(1):20815. doi: 10.1038/s41598-022-24636-1. PMID: 36460718Free PMC Article
Feenstra HM, Al-Khuzaei S, Shah M, Broadgate S, Shanks M, Kamath A, Yu J, Jolly JK, MacLaren RE, Clouston P, Halford S, Downes SM
Genes (Basel) 2022 Aug 10;13(8) doi: 10.3390/genes13081423. PMID: 36011334Free PMC Article
Gao FJ, Wang DD, Chen F, Sun HX, Hu FY, Xu P, Li J, Liu W, Qi YH, Li W, Wang M, Zhang S, Xu GZ, Chang Q, Wu JH
Br J Ophthalmol 2021 Jan;105(1):87-92. Epub 2020 Mar 18 doi: 10.1136/bjophthalmol-2020-315878. PMID: 32188678Free PMC Article

Diagnosis

Reurink J, Weisschuh N, Garanto A, Dockery A, van den Born LI, Fajardy I, Haer-Wigman L, Kohl S, Wissinger B, Farrar GJ, Ben-Yosef T, Pfiffner FK, Berger W, Weener ME, Dudakova L, Liskova P, Sharon D, Salameh M, Offenheim A, Heon E, Girotto G, Gasparini P, Morgan A, Bergen AA, Ten Brink JB, Klaver CCW, Tranebjærg L, Rendtorff ND, Vermeer S, Smits JJ, Pennings RJE, Aben M, Oostrik J, Astuti GDN, Corominas Galbany J, Kroes HY, Phan M, van Zelst-Stams WAG, Thiadens AAHJ, Verheij JBGM, van Schooneveld MJ, de Bruijn SE, Li CHZ, Hoyng CB, Gilissen C, Vissers LELM, Cremers FPM, Kremer H, van Wijk E, Roosing S
HGG Adv 2023 Apr 13;4(2):100181. Epub 2023 Jan 18 doi: 10.1016/j.xhgg.2023.100181. PMID: 36785559Free PMC Article
Karali M, Testa F, Di Iorio V, Torella A, Zeuli R, Scarpato M, Romano F, Onore ME, Pizzo M, Melillo P, Brunetti-Pierri R, Passerini I, Pelo E, Cremers FPM, Esposito G, Nigro V, Simonelli F, Banfi S
Sci Rep 2022 Dec 2;12(1):20815. doi: 10.1038/s41598-022-24636-1. PMID: 36460718Free PMC Article
Zaw K, Carvalho LS, Aung-Htut MT, Fletcher S, Wilton SD, Chen FK, McLenachan S
Asia Pac J Ophthalmol (Phila) 2022 Jul-Aug 01;11(4):369-379. Epub 2022 Aug 17 doi: 10.1097/APO.0000000000000546. PMID: 36041150
Gao FJ, Wang DD, Chen F, Sun HX, Hu FY, Xu P, Li J, Liu W, Qi YH, Li W, Wang M, Zhang S, Xu GZ, Chang Q, Wu JH
Br J Ophthalmol 2021 Jan;105(1):87-92. Epub 2020 Mar 18 doi: 10.1136/bjophthalmol-2020-315878. PMID: 32188678Free PMC Article
Koyanagi Y, Akiyama M, Nishiguchi KM, Momozawa Y, Kamatani Y, Takata S, Inai C, Iwasaki Y, Kumano M, Murakami Y, Omodaka K, Abe T, Komori S, Gao D, Hirakata T, Kurata K, Hosono K, Ueno S, Hotta Y, Murakami A, Terasaki H, Wada Y, Nakazawa T, Ishibashi T, Ikeda Y, Kubo M, Sonoda KH
J Med Genet 2019 Oct;56(10):662-670. Epub 2019 Jun 17 doi: 10.1136/jmedgenet-2018-105691. PMID: 31213501

Therapy

Gill JS, Theofylaktopoulos V, Mitsios A, Houston S, Hagag AM, Dubis AM, Moosajee M
Int J Mol Sci 2022 Apr 11;23(8) doi: 10.3390/ijms23084198. PMID: 35457016Free PMC Article
Hufnagel RB, Liang W, Duncan JL, Brewer CC, Audo I, Ayala AR, Branham K, Cheetham JK, Daiger SP, Durham TA, Guan B, Heon E, Hoyng CB, Iannaccone A, Kay CN, Michaelides M, Pennesi ME, Singh MS, Ullah E; Foundation Fighting Blindness Consortium Investigator Group
Hum Mutat 2022 May;43(5):613-624. Epub 2022 Mar 21 doi: 10.1002/humu.24365. PMID: 35266249Free PMC Article
Toms M, Dubis AM, de Vrieze E, Tracey-White D, Mitsios A, Hayes M, Broekman S, Baxendale S, Utoomprurkporn N, Bamiou D, Bitner-Glindzicz M, Webster AR, Van Wijk E, Moosajee M
Hum Mol Genet 2020 Jul 21;29(11):1882-1899. doi: 10.1093/hmg/ddaa004. PMID: 31998945Free PMC Article
Samanta A, Stingl K, Kohl S, Ries J, Linnert J, Nagel-Wolfrum K
Int J Mol Sci 2019 Dec 12;20(24) doi: 10.3390/ijms20246274. PMID: 31842393Free PMC Article
Vaché C, Besnard T, le Berre P, García-García G, Baux D, Larrieu L, Abadie C, Blanchet C, Bolz HJ, Millan J, Hamel C, Malcolm S, Claustres M, Roux AF
Hum Mutat 2012 Jan;33(1):104-8. Epub 2011 Nov 16 doi: 10.1002/humu.21634. PMID: 22009552

Prognosis

Sanjurjo-Soriano C, Jimenez-Medina C, Erkilic N, Cappellino L, Lefevre A, Nagel-Wolfrum K, Wolfrum U, Van Wijk E, Roux AF, Meunier I, Kalatzis V
HGG Adv 2023 Oct 12;4(4):100229. Epub 2023 Aug 7 doi: 10.1016/j.xhgg.2023.100229. PMID: 37654703Free PMC Article
Feenstra HM, Al-Khuzaei S, Shah M, Broadgate S, Shanks M, Kamath A, Yu J, Jolly JK, MacLaren RE, Clouston P, Halford S, Downes SM
Genes (Basel) 2022 Aug 10;13(8) doi: 10.3390/genes13081423. PMID: 36011334Free PMC Article
Gao FJ, Wang DD, Chen F, Sun HX, Hu FY, Xu P, Li J, Liu W, Qi YH, Li W, Wang M, Zhang S, Xu GZ, Chang Q, Wu JH
Br J Ophthalmol 2021 Jan;105(1):87-92. Epub 2020 Mar 18 doi: 10.1136/bjophthalmol-2020-315878. PMID: 32188678Free PMC Article
Vezinaw CM, Fishman GA, Chiang J
Doc Ophthalmol 2019 Apr;138(2):161-166. Epub 2019 Feb 22 doi: 10.1007/s10633-019-09677-8. PMID: 30796641
Testa F, Melillo P, Bonnet C, Marcelli V, de Benedictis A, Colucci R, Gallo B, Kurtenbach A, Rossi S, Marciano E, Auricchio A, Petit C, Zrenner E, Simonelli F
Retina 2017 Aug;37(8):1581-1590. doi: 10.1097/IAE.0000000000001389. PMID: 27828912

Clinical prediction guides

Sanjurjo-Soriano C, Jimenez-Medina C, Erkilic N, Cappellino L, Lefevre A, Nagel-Wolfrum K, Wolfrum U, Van Wijk E, Roux AF, Meunier I, Kalatzis V
HGG Adv 2023 Oct 12;4(4):100229. Epub 2023 Aug 7 doi: 10.1016/j.xhgg.2023.100229. PMID: 37654703Free PMC Article
Duncan JL, Liang W, Maguire MG, Porco TC, Wong J, Audo I, Cava JA, Grieve K, Kalitzeos A, Kreis J, Michaelides M, Norberg N, Paques M, Carroll J; Foundation Fighting Blindness Consortium Investigator Group
Am J Ophthalmol 2023 Aug;252:77-93. Epub 2023 Mar 21 doi: 10.1016/j.ajo.2023.03.006. PMID: 36948373
Tebbe L, Mwoyosvi ML, Crane R, Makia MS, Kakakhel M, Cosgrove D, Al-Ubaidi MR, Naash MI
Nat Commun 2023 Feb 21;14(1):972. doi: 10.1038/s41467-023-36431-1. PMID: 36810733Free PMC Article
Toms M, Dubis AM, de Vrieze E, Tracey-White D, Mitsios A, Hayes M, Broekman S, Baxendale S, Utoomprurkporn N, Bamiou D, Bitner-Glindzicz M, Webster AR, Van Wijk E, Moosajee M
Hum Mol Genet 2020 Jul 21;29(11):1882-1899. doi: 10.1093/hmg/ddaa004. PMID: 31998945Free PMC Article
Lenassi E, Vincent A, Li Z, Saihan Z, Coffey AJ, Steele-Stallard HB, Moore AT, Steel KP, Luxon LM, Héon E, Bitner-Glindzicz M, Webster AR
Eur J Hum Genet 2015 Oct;23(10):1318-27. Epub 2015 Feb 4 doi: 10.1038/ejhg.2014.283. PMID: 25649381Free PMC Article

Recent systematic reviews

Han JH, Cancellieri F, Perea-Romero I, Ayuso C, Quinodoz M, Rivolta C
Ophthalmic Res 2024;67(1):107-114. Epub 2023 Nov 28 doi: 10.1159/000535545. PMID: 38016437

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