Overview
Usher syndrome is the most common cause of combined deafblindness, accounting for approximately 50% of all deafblind individuals. It is an autosomal recessive condition characterized by sensorineural hearing loss and retinitis pigmentosa. Three clinical types are recognized: Type 1 (profound congenital deafness, vestibular dysfunction, RP onset in first decade), Type 2 (moderate-severe hearing loss, no vestibular dysfunction, RP onset in adolescence), and Type 3 (progressive hearing loss, variable vestibular dysfunction, variable RP onset).
Genetics
Usher syndrome is caused by mutations in at least 10 genes encoding proteins of the Usher interactome, a protein network critical for hair cell and photoreceptor function.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| MYO7A | 11q13.5 | AR | Myosin VIIA; most common Type 1 gene (~75% of USH1) |
| USH2A | 1q41 | AR | Usherin; most common Type 2 gene (~80% of USH2); also causes RP without hearing loss |
| ADGRV1 (GPR98) | 5q14.3 | AR | Adhesion G protein-coupled receptor V1; Type 2B |
| WHRN (DFNB31) | 9q32 | AR | Whirlin; Type 2D |
| CLRN1 | 3q25.1 | AR | Clarin-1; Type 3A |
Clinical Presentation
Type 1 (most severe)
- Profound congenital sensorineural hearing loss
- Vestibular dysfunction (delayed motor milestones)
- RP onset in first decade of life
Type 2 (most common)
- Moderate to severe hearing loss (stable)
- Normal vestibular function
- RP onset in adolescence
Type 3
- Progressive hearing loss (post-lingual)
- Variable vestibular dysfunction
- Variable RP onset and progression
Diagnosis
- Audiological evaluation: Audiogram showing characteristic hearing loss pattern by type
- Vestibular testing: Electronystagmography or vestibular evoked myogenic potentials
- ERG: Reduced rod and cone responses; may be normal early in Type 2
- Visual field testing: Peripheral constriction
- Fundus examination: RP features (bone spicules, vessel attenuation, disc pallor)
- Genetic testing: Comprehensive USH gene panel (10+ genes)
Current Research & Treatment
Gene therapy trials are underway for MYO7A (UshStat, lentiviral vector) and CLRN1 mutations. Antisense oligonucleotide approaches for USH2A exon 13 mutations are in Phase 1/2 trials (QR-421a/sepofarsen). The dual challenge of treating both hearing and vision loss makes Usher syndrome a complex but active area of therapeutic development.
Active Clinical Trials
The following active clinical trials are investigating treatments for Usher Syndrome. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.
Sepul Bio · ASO targeting USH2A exon 13
BlueRock Therapeutics · iPSC-derived photoreceptor cell therapy
Johns Hopkins University · Oral antioxidant (gene-agnostic)
Supporting Organizations
The following nonprofit organizations fund research, support patients, and advocate for advances in the treatment and cure of Usher Syndrome.
Foundation Fighting Blindness
VisitThe world's leading funder of IRD research since 1971.
$954M+ raised since 1971Usher Syndrome Coalition
VisitThe most comprehensive resource for the global Usher syndrome community.
Global leader in Usher syndrome advocacyUsher Syndrome Society
VisitRaising awareness and research funds for every type of Usher syndrome.
Focused on all Usher syndrome typesUsher 1F Collaborative
VisitFunding research to save or restore vision in Usher syndrome type 1F.
$14M+ secured for USH1F researchRetina International
VisitA patient-led global umbrella NGO for retinal disease communities worldwide.
34+ national societies worldwideHearing Health Foundation (HHF)
VisitFunding research for hearing loss and Usher syndrome through the ERG program.
Annual ERG grants for Usher syndrome researchFighting Blindness Canada
VisitLeading the fight against blindness by funding IRD research in Canada.
Canada's leading IRD research funderRetina UK
VisitFunding research and supporting people affected by inherited sight loss in the UK.
UK's leading inherited sight loss charity