Auditory and olfactory findings in patients with USH2A-related retinal degeneration-Findings at baseline from the rate of progression in USH2A-related retinal degeneration natural history study (RUSH2A)

Am J Med Genet A. 2021 Dec;185(12):3717-3727. doi: 10.1002/ajmg.a.62437. Epub 2021 Jul 30.


Sensorineural hearing loss (SNHL) is characteristic of Usher syndrome type 2 (USH2), but less is known about SNHL in nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) and olfaction in USH2A-associated retinal degeneration. The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) is a natural history study that enrolled 127 participants, 80 with USH2 and 47 with ARRP. Hearing was measured by pure-tone thresholds and word recognition scores, and olfaction by the University of Pennsylvania Smell Identification Test (UPSIT). SNHL was moderate in 72% of USH2 participants and severe or profound in 25%, while 9% of ARRP participants had moderate adult-onset SNHL. Pure-tone thresholds worsened with age in ARRP but not in USH2 participants. The degree of SNHL was not associated with other participant characteristics in either USH2 or ARRP. Median pure-tone thresholds in ARRP participants were significantly higher than the normative population (p < 0.001). Among 14 USH2 participants reporting newborn hearing screening results, 7 reported passing. Among RUSH2A participants, 7% had mild microsmia and 5% had moderate or severe microsmia. Their mean (±SD) UPSIT score was 35 (±3), similar to healthy controls (34 [±3]; p = 0.39). Olfaction differed by country (p = 0.02), but was not significantly associated with clinical diagnosis, age, gender, race/ethnicity, smoking status, visual measures, or hearing. Hearing loss in USH2A-related USH2 did not progress with age. ARRP patients had higher pure-tone thresholds than normal. Newborn hearing screening did not identify all USH2A-related hearing loss. Olfaction was not significantly worse than normal in participants with USH2A-related retinal degeneration.

Keywords: Usher syndrome type 2; autosomal recessive retinitis pigmentosa; olfaction; sensorineural hearing loss.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / pathology
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Retinal Degeneration / diagnosis
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology
  • Smell / genetics
  • Usher Syndromes / diagnosis
  • Usher Syndromes / genetics*
  • Usher Syndromes / pathology
  • Young Adult


  • Extracellular Matrix Proteins
  • USH2A protein, human

Supplementary concepts

  • Usher syndrome, type 2A