What is Usher syndrome type 3?

Usher Syndrome Type 3: Clinical Features and Management

Usher syndrome type 3 (USH3) is a rare form of Usher syndrome characterized by progressive postlingual hearing loss, variable onset of retinitis pigmentosa, and variable vestibular function, which requires early diagnosis and intervention to minimize morbidity and mortality associated with combined sensory deficits. 1, 2

Clinical Characteristics of Usher Syndrome Type 3

USH3 differs from other Usher syndrome types in several key aspects:

• Hearing Loss: Progressive postlingual hearing loss (unlike congenital hearing loss in USH1 and USH2)
• Vision Loss: Variable onset retinitis pigmentosa
• Vestibular Function: Variable vestibular response (compared to vestibular areflexia in USH1 and normal function in USH2)
• Genetics: Primarily caused by mutations in the USH3A (CLRN1) gene 2, 3
• Prevalence: Generally rare worldwide (approximately 2% of all Usher syndrome cases), but shows higher prevalence in certain populations, particularly in Finland where it accounts for up to 42% of Usher syndrome cases 4

Diagnostic Approach

Early diagnosis is critical for appropriate intervention and management:

1. Audiological Assessment:

   • Serial audiometric evaluations to document progressive hearing loss
   • Speech discrimination testing
   • Tympanometry and acoustic reflex testing

2. Ophthalmological Evaluation:

   • Comprehensive eye examination
   • Electroretinography to assess retinal function
   • Visual field testing to detect peripheral vision loss
   • Fundoscopic examination to identify retinitis pigmentosa 1

3. Vestibular Testing:

   • Assessment of balance function
   • Electronystagmography or video head impulse testing

4. Genetic Testing:

   • Molecular genetic testing for USH3A (CLRN1) gene mutations
   • Comprehensive testing of other Usher syndrome genes if USH3A testing is negative 1, 3

Management Strategies

Management focuses on addressing hearing and vision loss:

Hearing Management

• Early intervention with hearing aids for mild to moderate hearing loss
• Consideration of cochlear implantation as hearing loss progresses
• Speech-language therapy to maintain communication skills
• Assistive listening devices for school and work environments 1

Vision Management

• Regular ophthalmologic monitoring for progression of retinitis pigmentosa
• Vitamin A supplementation may be beneficial in slowing retinal degeneration 1
• Low vision aids and services
• Orientation and mobility training
• Consideration of emerging therapies in clinical trials 5

Multidisciplinary Care

• Genetic counseling for family planning (autosomal recessive inheritance)
• Psychological support for adjustment to progressive sensory loss
• Educational and vocational support
• Balance training if vestibular dysfunction is present

Emerging Therapeutic Approaches

Several therapeutic strategies are in development:

• Gene replacement therapy
• Antisense oligonucleotides
• Gene editing approaches
• Small molecule drugs
• Cell-based therapies 5

Important Clinical Considerations

1. Progressive Nature: Unlike USH1 and USH2, the progressive nature of hearing loss in USH3 requires regular monitoring and adjustment of interventions.

2. Variability: Significant phenotypic variability exists within USH3, even among patients with the same genetic mutations.

3. Psychological Impact: The progressive nature of sensory loss can have significant psychological impacts, requiring ongoing support.

4. Early Intervention: Early diagnosis and intervention are crucial for optimizing outcomes and quality of life.

5. Regular Follow-up: Patients require regular audiological and ophthalmological follow-up to monitor disease progression and adjust interventions accordingly 1.

By understanding the unique features of USH3 and implementing appropriate interventions, healthcare providers can significantly improve outcomes and quality of life for affected individuals.