Usher Syndrome

often abbreviated as USH

• Retinitis Pigmentosa
• Sensorineural hearing loss
• Vestibular disturbances

• Retinitis Pigmentosa
  • Pigmentary retinopathy with degeneration of the RPE
  • Optic disc pallor
  • Retinal arteriolar attenuation
  • Symptoms
    • Decreased visual acuity
    • Nyctalopia
    • Peripheral visual field deterioration

• Progressive retinal degeneration, course depends on the gene affected
  • USH type 1 = profound congenital hearing loss and early vision loss
  • USH type 2 = RP by the second decade, moderate to severe congenital hearing loss and no vestibular abnormalities
  • USH type 3 = Progressive and variable hearing loss, RP and vestibular abnormalities
  • Significant overlap among subtypes

• Autosomal Recessive inheritance
• Included in the category of ciliopathy
  • abnormal formation of cilia
• Major genes affected
  • USH1 genes
    • MYO7A, USH1C, PDCH15, CDH23, USH1G
  • USH2 genes
    • USH2A, ADGRV1, WHRN
  • USH3 gene- CLRN1
• Other genes implicated but need classification
• Usher genes encode for proteins expressed in the inner ear and retina where they provide essential functions for the development of sensory hair cells and photoreceptor maintenance

From Resource (1)

• Prevalence
  • Worldwide 4-17 per 100,000
  • USA 4.4 per 100,000 (1 in 22,700)
• Most common cause for hereditary deafness and blindness
  • 5% of all congenital deafness
  • 18% of retinitis pigmentosa cases

1. Delmanghani S et al. The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification. Human Genetics 2022;141:709-735